Guttorm Haraldsen

Professor II - Avdeling for patologi

English version of this page

E-post guttorm.haraldsen@medisin.uio.no

Rom A3.M016

Brukernavn

Besøksadresse Sognsvannsveien 20 Rikshospitalet 0372 Oslo

Postadresse Postboks 4950 Nydalen OUS HF Rikshospitalet 0424 Oslo

Pressebilde Last ned visittkort

Faglige interesser

Inflammation, anigogenesis, tissue repair, vascular and cytokine biology

Bakgrunn

MD University of Bonn 1989
PhD University of Oslo 1997

Total career publications (PubMed indexed): 82
Google Scholar profile, 23FEB2021: Citations 9583 times, H-index: 44
Publications include papers in Nature (1x), Immunity (2x), Cancer Cell (1x), Gastroenterology (1x), Gut (3x), J Exp Med (4x), Hepatology (1x), Blood (5x), Trends Immunol (3x), PNAS (1x), Nature Communications (1x), J Invest Dermatol (2x), ATVB (2x), Am J Transplant (1x), J Immunol (4x), Am J Pathol (6x) and J. Biol. Chem(1x).
Research Director, Division of Diagnostics and Intervention, Oslo University Hospital, 2010-2013
Research Director, Division of Pathology, Rikshospitalet University Hospital 2005-2009
Biobank coordinator/Senior Scientist, Rikshospitalet 2005
Senior Scientist, Department of Pathology, Rikshospitalet 2002-2004
Visiting Scientist, Novartis Research Institute, Vienna 2001-2002
Scientist, Inst. of Pathology, University of Oslo 2000-2002
Postdoctoral Fellow, Inst. of Pathology, University of Oslo
Postdoctoral Fellow, Dept of Pathology (head, prof. E.C. Butcher, MD), Stanford University, Stanford, CA, 1997-1998
Research Fellow, Inst. of Pathology (head, prof. P. Brandtzaeg, PhD), Univ. of Oslo, 1992-1997

Priser

2020 Professor Kreyberg’s prize of Experimental Pathology 2017-2020 to Olav Sundnes for his PhD Thesis (supervisor: Guttorm Haraldsen)

2016 Professor Kreyberg’s prize of Experimental Pathology 2013-2016 to Eirik Sundlisæter for his PhD Thesis (supervisor: Guttorm Haraldsen)

2008 Professor Kreyberg’s prize of Experimental Pathology 2005-2008 to Dag Kristian Skovseth for his PhD Thesis (supervisor: Guttorm Haraldsen)

2000-2005 Career Investigator, Research Council of Norway

1999, 2000, 2001 Odd Fellow Medical Award

Samarbeid

Espen Haavardsholm, Diakonhjemmets sykehus
Hilde Berner Hammer, Diakonhjemmets sykehus
Chris Siebel, Genentech Inc, South San Francisco
Ralph Adams, Max-Planck Institut, Münster
Martin Knöfler, University of Vienna
Kim Midwood, Oxford University
Stefan Pflanz, Merck Research Labs (former DNAX), Palo Alto
Pål Aukrust, OUS
Alexandre Corthay, OUS
Bjørn Dahlhus, OUS
Zlatko Dembic, Oralbiologi, UiO
Jon Florholmen, UNP
Pål-Dag Line, OUS
Kjetil Taskén, Bioteknologisenteret
Morten Vatn, OUS/Ahus

Twenty most important publications:

Pietka W, Khnykin D, Bertelsen V, Lossius AH, Stav-Noraas TE, Hol Fosse J, Galtung HK, Haraldsen G*, Sundnes O. Hypo-osmotic stress drives IL-33 production in human keratinocytes-an epidermal homeostatic response. J Invest Dermatol 2019; 139:81-90 30120934
*corresponding author, cited: 1
Poulsen LC, Edelmann RJ, Krüger S, Diégues-Hurtado R, Shah A, Stav-Noraas, Renzi A, Szymanska M, Wang J, Ehling M, Benedito R, Kasprzycka M, Bækkevold E, Sundnes O, Midwood K, Scott H, Collas P, Siebel CW, Adams RH, Haraldsen G*, Hol J, Sundlisæter E. Inhibition of endothelial notch1 signaling attenuates inflammation by reducing cytokine-mediated histone acetylation at inflammatory enhancers. Arterioscler Thromb Vasc Biol. 2018;38:854-869 29449332
*corresponding author, cited: 5
Stav-Noraas TE, Edelmann RJ, Poulsen LC, Sundnes O, Phung D, Küchler AM, Müller F, Kamen AA, Haraldsen G*, Kaarbø M, Hol J. Endothelial IL-33 expression is augmented by adenoviral activation of the dna damage machinery. J Immunol. 2017; 198:3318-3325 28258201
*corresponding author, cited: 5
Sundnes O, Pietka W, Loos T, Sponheim J, Rankin AL, Pflanz S, Bertelsen V, Sitek JC, Hol J, Haraldsen G*, Khnykin D. Epidermal expression and regulation of interleukin-33 during homeostasis and inflammation: strong species differences. J Invest Dermatol 2015; 135:1771-80 25739051
*corresponding author, cited: 15
Pollheimer J, Balogh J, Jetne R, Skånland SS, Sponheim J, Brox MJ, Sundlisæter E, Loos T, Vatn M, Kasprzycka M, Wang J, Küchler AM, Taskén K, Haraldsen G*, Hol J. Interleukin-33 drives a proinflammatory endothelial activation that selectively targets non-quiescent cells. Arterioscler Thromb Vasc Biol 2013,33:e47-55 23162017
*corresponding author, cited: 44
Sundlisæter E, Jetne R, Hol J, Sponheim J, Küchler AM, Weiss M, Udalova IA, Midwood KS, Kasprzycka M, Haraldsen G. The alarmin interleukin‑33 is a Notch target in quiescent endothelial cells. Am J Pathol 2012; 181:1099-1111 22809957 Cited: 60
Sponheim J, Pollheimer J, Olsen T, Balogh J, Hammarström C, Sørensen DR, Røed Nilsen H, Küchler AM, Vatn M, Haraldsen G. Inflammatory bowel disease-associated interleukin‑33 is preferentially expressed in ulceration-associated myofibroblasts. Am J Pathol 2010; 177: 2804-15 21037074 Cited: 147
Mikalsen B, Fosby B, Wang J, Hammarström C, Bjærke H, Lundström M, Kasprzycka M, Scott H, Line PD Haraldsen G. Genome-wide transcription profiles of endothelial cells during cardiac allograft rejection. Am J Transplantation 2010; 10: 1534–44 20642680 Cited: 8
Haraldsen G, Balogh J, Pollheimer J, Sponheim J, Kuchler AM. Interleukin-33 – cytokine of dual function or novel alarmin? Trends Immunol. 2009; 30:227-33 19359217 Cited: 348
Küchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G. Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation. Am J Pathology, 2008; 173:1229-1242 18787100 Cited: 233
Corthay A, Skovseth DK, Lundin K, Røsjø E, Hofgaard P, Omholt H, Haraldsen G, Bogen B. Primary antitumor immune response mediated by CD4(+) T cells. Immunity, 2005; 22:371-83 15780993 Cited: 361
Skovseth DK, Veuger M, Sorensen DR, DeAngelis P, Haraldsen G. Endostatin dramatically inhibits endothelial cell migration, vascular morphogenesis and perivascular cell recruiment in vivo. Blood 2005; 105:1044-1051 15466935 Cited: 113
Øynebraten I, Bakke O, Brandtzaeg P, Johansen FE, Haraldsen G. Rapid chemokine secretion from endothelial cells originates from two distinct compartments. Blood, 2004; 104:314-320 15044249 Cited: 133
Chi J-T, Chang HY, Haraldsen G, Jahnsen FL, Troyanska OG, Chang DS, Wang Z, Rockson SG, Botstein D, Brown PO. Endothelial cell diversity revealed by global expression profiling PNAS 2003; 100:10623-10628 12963823 Cited: 775
Baekkevold ES, Roussigné M, Yamanaka T, Johansen FE, Jahnsen FL, Amalric F, Brandtzaeg P, Erard M, Haraldsen G*, Girard JP*. Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules. Am J Pathol 2003; 163:69-79 12819012 *shared corresponding authors, Cited: 515
Baekkevold ES, Yamanaka T, Palframan R, Carlsen H, Reinholt FP, von Andrian U, Brandtzaeg P, Haraldsen G. The CCR7-ligand ELC (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. J Exp Med 2001; 193:1105-1112 11342595 Cited: 434
Haraldsen^.G*, Kunkel EJ*, Campbell JJ*, Pan J, Vierra MA, Goodman SC, Wardlaw AJ, Genovese MC, Parker CM, Butcher EC, Andrew DP, Agace WW. Lymphocyte CC Chemokine Receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. J Exp Med 2000; 192:761-768 (*shared first authors, GH is listed first to emphasize) 10974041 Cited: 676
Campbell JJ, Haraldsen G, Pan J, Rottman J, Qin S, Ponath P, Andrew DP, Warnke R, Ruffing N, Kassam N, Wu L, Butcher EC. The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 1999; 400:776-780 10466728 Cited: 931
Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G. Rapid secretion of prestored intracellular interleukin-8 from Weibel-Palade bodies of microvascular endothelial cells. J Exp Med 1998;188:1751-6 9802986 Cited: 271
Haraldsen G, Kvale D, Lien B, Farstad IN, Brandtzaeg P. Cytokine-regulated expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in human intestinal microvascular endothelial cells. J Immunol 1996;156:2558-65 8786319 Cited: 470

Theses

Haraldsen G: Expression and specific quantitative change of multiple capillary phenotypes in polymyositis and non-inflammatory muscle diseases. Doctoral thesis. University of Bonn, 10.06.1992
Haraldsen G: Functional studies of cultured human gut endothelium. Characterization of biological properties with special reference to inflammatory bowel disease. Doctoral thesis. University of Oslo, 1997 (includes publications A4, A5, A6, A8, and A10 in addition to an Introduction of 17 pp)

Patents

Girard, JP, Erard M, Aguilar L, Haraldsen, G, Bækkevold E, Veuger M, Brandtzaeg P. "NF-HEV (IL-33) compositions and methods of use" WO 2004/056868 A2, filed 08.07.2004.

Disclosures of invention (DOFI)

Haraldsen G, Krüger S. Novel antibodies to treat chronic inflammatory diseases. JUN2020
Sundlisæter E, Haraldsen G. Behandling av de vanligste årsaker til blindhet (diabetisk øyesykdom og makuladegenerasjon) uten gjentatte sprøytestikk i øyet hver 4. uke. 10.02.2011
Haraldsen G, Skovseth DK, Sørensen DR. Dyremodell for terapieffekt av in vivo angiogenese. 22.10.2004Haraldsen G, Skovseth DK. Veuger M, Küchler A. Novel anti-angiogenic targets. 18.10.2004

Stabell, Siri Hansen; Renzi, Anastasia; Nilsen, Hogne Røed; Antonsen, Olaf Harald; Fosse, Johanna Hol & Haraldsen, Guttorm [Vis alle 7 forfattere av denne artikkelen] (2023). Detection of native, activated Notch receptors in normal human apocrine-bearing skin and in hidradenitis suppurativa. Experimental Dermatology. ISSN 0906-6705. 33(1). doi: 10.1111/exd.14977. Fulltekst i vitenarkiv
gjølberg, torleif; Wik, Jonas Aakre; Johannessen, Hanna; Krüger, Stig; Bassi, Nicola & Christopoulos, Panagiotis [Vis alle 15 forfattere av denne artikkelen] (2023). Antibody blockade of Jagged1 attenuates choroidal neovascularization. Nature Communications. ISSN 2041-1723. 14(1). doi: 10.1038/s41467-023-38563-w. Fulltekst i vitenarkiv
Gundersen, Mona Dixon; Larsen, Kenneth Bowitz; Johnsen, Kay-Martin; Goll, Rasmus; Florholmen, Jon & Haraldsen, Guttorm (2022). Hypo-osmotic stress induces the epithelial alarmin IL-33 in the colonic barrier of ulcerative colitis. Scientific Reports. ISSN 2045-2322. 12:11550(1), s. 1–12. doi: 10.1038/s41598-022-15573-0. Fulltekst i vitenarkiv
Christopoulos, Panagiotis; Gjølberg, Torleif Tollefsrud; Krüger, Stig; Haraldsen, Guttorm; Andersen, Jan Terje & Sundlisæter, Eirik (2021). Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases. Frontiers in Immunology. ISSN 1664-3224. 12:668207, s. 1–22. doi: 10.3389/fimmu.2021.668207. Fulltekst i vitenarkiv
Fjær, Roar; Marciniak, Katarzyna; Sundnes, Olav; Hjorthaug, Hanne; Sheng, Ying & Hammarström, Clara Louise [Vis alle 18 forfattere av denne artikkelen] (2021). A novel somatic mutation in GNB2 provides new insights to the pathogenesis of Sturge-Weber syndrome. Human Molecular Genetics. ISSN 0964-6906. 30(21), s. 1919–1931. doi: 10.1093/hmg/ddab144. Fulltekst i vitenarkiv Vis sammendrag
Sturge–Weber syndrome (SWS) is a neurocutaneous disorder characterized by vascular malformations affecting skin, eyes and leptomeninges of the brain, which can lead to glaucoma, seizures and intellectual disability. The discovery of a disease-causing somatic missense mutation in the GNAQ gene, encoding an alpha chain of heterotrimeric G-proteins, has initiated efforts to understand how G-proteins contribute to SWS pathogenesis. The mutation is predominantly detected in endothelial cells and is currently believed to affect downstream MAPK signalling. In this study of six Norwegian patients with classical SWS, we aimed to identify somatic mutations through deep sequencing of DNA from skin biopsies. Surprisingly, one patient was negative for the GNAQ mutation, but instead harbored a somatic mutation in GNB2 (NM_005273.3:c.232A>G, p.Lys78Glu), which encodes a beta chain of the same G-protein complex. The positions of the mutant amino acids in the G-protein are essential for complex reassembly. Therefore, failure of reassembly and continuous signalling is a likely consequence of both mutations. Ectopic expression of mutant proteins in endothelial cells revealed that expression of either mutant reduced cellular proliferation, yet regulated MAPK signalling differently, suggesting that dysregulated MAPK signalling cannot fully explain the SWS phenotype. Instead, both mutants reduced synthesis of Yes-associated protein (YAP), a transcriptional co-activator of the Hippo signalling pathway, suggesting a key role for this pathway in the vascular pathogenesis of SWS. The discovery of the GNB2 mutation sheds novel light on the pathogenesis of SWS and suggests that future research on targets of treatment should be directed towards the YAP, rather than the MAPK, signalling pathway.
Lossius, Astrid Haaskjold; Sundnes, Olav; Ingham, Anna Cäcilia; Edslev, Sofie Marie; Bjørnholt, Jørgen Vildershøj & Lilje, Berit [Vis alle 12 forfattere av denne artikkelen] (2021). Shifts in the Skin Microbiota after UVB Treatment in Adult Atopic Dermatitis. Dermatology. ISSN 1018-8665. 238(1), s. 109–120. doi: 10.1159/000515236. Fulltekst i vitenarkiv
Hol, Johanna; Haraldsen, Guttorm; Falk, Knut & Edelmann, Reidunn Jetne (2021). Endothelial Cells in Emerging Viral Infections. Frontiers in Cardiovascular Medicine. ISSN 2297-055X. 8, s. 1–23. doi: 10.3389/fcvm.2021.619690. Fulltekst i vitenarkiv
Li, Gaoyang; Kolan, Shrikant; Guo, Shuai; Marciniak, Katarzyna; Kolan, Pratibha Shrikant & Malachin, Giulia [Vis alle 9 forfattere av denne artikkelen] (2021). Activated, Pro-Inflammatory Th1, Th17, and Memory CD4+ T Cells and B Cells Are Involved in Delayed-Type Hypersensitivity Arthritis (DTHA) Inflammation and Paw Swelling in Mice. Frontiers in Immunology. ISSN 1664-3224. 12, s. 1–15. doi: 10.3389/fimmu.2021.689057. Fulltekst i vitenarkiv
Wik, Jonas Aakre; Phung, Danh; Kolan, Shrikant; Haraldsen, Guttorm; Skålhegg, Bjørn Steen & Hol Fosse, Johanna (2021). Inflammatory activation of endothelial cells increases glycolysis and oxygen consumption despite inhibiting cell proliferation. FEBS Open Bio. ISSN 2211-5463. 11(6), s. 1719–1730. doi: 10.1002/2211-5463.13174. Fulltekst i vitenarkiv
Sundnes, Olav; Ottestad, William Arne; Schjalm, Camilla; Lundbäck, Peter; La Cour Poulsen, Lars & Mollnes, Tom Eirik [Vis alle 8 forfattere av denne artikkelen] (2021). Rapid systemic surge of IL-33 after severe human trauma: a prospective observational study. Molecular medicine (Cambridge, Mass. Print). ISSN 1076-1551. 27:29, s. 1–10. doi: 10.1186/s10020-021-00288-1. Fulltekst i vitenarkiv
Gatti, Francesca; Mia, Sobuj; Hammarström, Clara Louise; Frerker, Nadine; Fosby, Bjarte & Wang, Junbai [Vis alle 11 forfattere av denne artikkelen] (2021). Nuclear IL-33 restrains the early conversion of fibroblasts to an extracellular matrix-secreting phenotype. Scientific Reports. ISSN 2045-2322. 11:108(1), s. 1–13. doi: 10.1038/s41598-020-80509-5. Fulltekst i vitenarkiv
Lossius, Astrid Haaskjold; Berents, Teresa Løvold; Sætre, Frank Ove; Nilsen, Hogne Røed; Bradley, Maria & Asad, Samina [Vis alle 9 forfattere av denne artikkelen] (2020). Early transcriptional changes after UVB treatment in atopic dermatitis includes inverse regulation of IL‐36γ and IL‐37. Experimental Dermatology. ISSN 0906-6705. 30(2), s. 249–261. doi: 10.1111/exd.14217. Fulltekst i vitenarkiv
Lu, Yuning; Basatemur, Gemma; Scott, Ian C.; Chiarugi, Davide; Clement, Marc & Harrison, James [Vis alle 19 forfattere av denne artikkelen] (2020). Interleukin-33 Signaling Controls the Development of Iron-Recycling Macrophages. Immunity. ISSN 1074-7613. 52(5), s. 782–793.e5. doi: 10.1016/j.immuni.2020.03.006.
Wik, Jonas Aakre; Lundbäck, Peter; La Cour Poulsen, Lars; Haraldsen, Guttorm; Skålhegg, Bjørn Steen & Hol, Johanna (2020). 3PO inhibits inflammatory NFκB and stress-activated kinase signaling in primary human endothelial cells independently of its target PFKFB3. PLOS ONE. ISSN 1932-6203. 15:e0229395(3), s. 1–18. doi: 10.1371/journal.pone.0229395. Fulltekst i vitenarkiv
Pihlstrøm, Hege; Ueland, Thor; Michelsen, Annika; Aukrust, Pål; Gatti, Francesca & Hammarström, Clara Louise [Vis alle 15 forfattere av denne artikkelen] (2020). Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients. PLOS ONE. ISSN 1932-6203. 15:e0243759(12), s. 1–14. doi: 10.1371/journal.pone.0243759. Fulltekst i vitenarkiv
Pietka, Wojciech; Sundnes, Olav; Hammarström, Clara Louise; Zucknick, Manuela; Khnykin, Denis & Haraldsen, Guttorm (2020). Lack of interleukin-33 and its receptor does not prevent calcipotriol-induced atopic dermatitis-like inflammation in mice. Scientific Reports. ISSN 2045-2322. 10:6451, s. 1–8. doi: 10.1038/s41598-020-63410-z. Fulltekst i vitenarkiv
Ottestad, William Arne; Rognes, Ingrid Nygren; Skaga, Erlend; Frisvoll, Cassandra; Haraldsen, Guttorm & Eken, Torsten [Vis alle 7 forfattere av denne artikkelen] (2019). HMGB1 concentration measurements in trauma patients: assessment of pre-analytical conditions and sample material. Molecular medicine (Cambridge, Mass. Print). ISSN 1076-1551. 26:5(1), s. 1–8. doi: 10.1186/s10020-019-0131-0. Fulltekst i vitenarkiv
Pietka, Wojciech; Khnykin, Denis; Bertelsen, Vibeke; Lossius, Astrid Haaskjold; Stav-Noraas, Tor Espen & Hol, Johanna [Vis alle 9 forfattere av denne artikkelen] (2018). Hypo-osmotic stress drives IL-33 production in human keratinocytes - An epidermal homeostatic response. Journal of Investigative Dermatology. ISSN 0022-202X. 139(1), s. 81–90. doi: 10.1016/j.jid.2018.07.023. Fulltekst i vitenarkiv
La Cour Poulsen, Lars; Edelmann, Reidunn Jetne; Krüger, Stig; Diéguez-Hurtado, Rodrigo; Shah, Akshay & Stav-Noraas, Tor Espen [Vis alle 22 forfattere av denne artikkelen] (2018). Inhibition of endothelial NOTCH1 signaling attenuates inflammation by reducing cytokine-mediated histone acetylation at inflammatory enhancers . Arteriosclerosis, Thrombosis and Vascular Biology. ISSN 1079-5642. 38(4), s. 854–869. doi: 10.1161/ATVBAHA.117.310388. Fulltekst i vitenarkiv
Stav-Noraas, Tor Espen; Edelmann, Reidunn Jetne; La Cour Poulsen, Lars; Sundnes, Olav; Phung, Danh & Kuchler, Axel Matthias [Vis alle 11 forfattere av denne artikkelen] (2017). Endothelial IL-33 expression is augmented by adenoviral activation of the DNA damage machinery. Journal of Immunology. ISSN 0022-1767. 198(8), s. 3318–3325. doi: 10.4049/jimmunol.1600054. Fulltekst i vitenarkiv
Pihlstrøm, Hege; Gatti, Francesca; Hammarström, Clara Louise; Eide, Ivar Anders; Kasprzycka, Monika & Wang, Junbai [Vis alle 13 forfattere av denne artikkelen] (2017). Early introduction of oral paricalcitol in renal transplant recipients. An open-label randomized study. Transplant International. ISSN 0934-0874. 30(8), s. 827–840. doi: 10.1111/tri.12973.
Pihlstrøm, Hege; Mjøen, Geir; Mucha, S; Haraldsen, Guttorm; Franke, A & Jardine, A [Vis alle 9 forfattere av denne artikkelen] (2016). Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study. American Journal of Transplantation. ISSN 1600-6135. 17(2), s. 528–533. doi: 10.1111/ajt.13995.
Cantelmo, Anna Rita; Conradi, Lena-Christin; Brajic, Aleksandra; Goveia, Jermaina; Kalucka, Joanna & Pircher, Andreas [Vis alle 34 forfattere av denne artikkelen] (2016). Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy. Cancer Cell. ISSN 1535-6108. 30(6), s. 968–985. doi: 10.1016/j.ccell.2016.10.006.
Lorvik, Kristina Berg; Hammarström, Clara Louise; Fauskanger, Marte; Haabeth, Ole Audun; Zangani, Michael M & Haraldsen, Guttorm [Vis alle 8 forfattere av denne artikkelen] (2016). Adoptive transfer of tumor-specific Th2 cells eradicates tumors by triggering an in situ inflammatory immune response. Cancer Research. ISSN 0008-5472. 76(23), s. 6864–6876. doi: 10.1158/0008-5472.CAN-16-1219.
Gundersen, Mona Dixon; Goll, Rasmus; Hol, Johanna; Olsen, Trine; Rismo, Renathe & Sørbye, Sveinung Wergeland [Vis alle 9 forfattere av denne artikkelen] (2016). Loss of interleukin 33 expression in colonic crypts - a potential marker for disease remission in ulcerative colitis. Scientific Reports. ISSN 2045-2322. 6. doi: 10.1038/srep35403. Fulltekst i vitenarkiv
Kasprzycka, Monika; Hammarström, Clara Louise & Haraldsen, Guttorm (2015). Tenascins in fibrotic disorders-from bench to bedside. Cell Adhesion & Migration. ISSN 1933-6918. 9(1-2), s. 83–89. doi: 10.4161/19336918.2014.994901.
Schrumpf, Elisabeth; Tan, Corey; Karlsen, Tom Hemming; Sponheim, Jon; Björkström, Niklas K. & Sundnes, Olav [Vis alle 16 forfattere av denne artikkelen] (2015). The biliary epithelium presents antigens to and activates natural killer T cells. Hepatology. ISSN 0270-9139. 62(4), s. 1249–1259. doi: 10.1002/hep.27840.
Sundnes, Olav; Pietka, Wojciech; Loos, Tamara; Sponheim, Jon; Rankin, Andrew L. & Pflanz, Stefan [Vis alle 11 forfattere av denne artikkelen] (2015). Epidermal expression and regulation of interleukin-33 during homeostasis and inflammation: Strong species differences. Journal of Investigative Dermatology. ISSN 0022-202X. 135(7), s. 1771–1780. doi: 10.1038/jid.2015.85.
Øynebråten, Inger; Barois, Nicolas; Bergeland, Trygve; Kuchler, Axel Matthias; Bakke, Oddmund & Haraldsen, Guttorm (2015). Oligomerized, filamentous surface presentation of RANTES/CCL5 on vascular endothelial cells. Scientific Reports. ISSN 2045-2322. 5:9261. doi: 10.1038/srep09261. Fulltekst i vitenarkiv
Tveita, Anders; Schjesvold, Fredrik Hellem; Sundnes, Olav; Haabeth, Ole Audun; Haraldsen, Guttorm & Bogen, Bjarne (2014). Indirect CD4+ T-cell-mediated elimination of MHC II(NEG) tumor cells is spatiallyrestricted and fails to prevent escape of antigen-negative cells. European Journal of Immunology. ISSN 0014-2980. 44(9), s. 2625–2637. doi: 10.1002/eji.201444659.
Skårn, Magne Nordang; Noordhuis, Paul; Wang, Mengyu; Veuger, Maria Johanna; Kresse, Stine Henrichson & Egeland, Eivind Valen [Vis alle 15 forfattere av denne artikkelen] (2014). Generation and characterization of an immortalized human mesenchymal stromal cell line. Stem Cells and Development. ISSN 1547-3287. 23(19), s. 2377–2389. doi: 10.1089/scd.2013.0599.
Pandya, Abhilash D.; Leergaard, Trygve Brauns; Dissen, Erik; Haraldsen, Guttorm & Spurkland, Anne (2014). Expression of the T cell-specific adapter protein in human tissues. Scandinavian Journal of Immunology. ISSN 0300-9475. 80(3), s. 169–179. doi: 10.1111/sji.12199.
Pollheimer, Jürgen; Bodin, Johanna; Sundnes, Olav; Bekkeheien, Reidunn C; Skånland, Sigrid Strand & Sponheim, Jon [Vis alle 16 forfattere av denne artikkelen] (2013). Interleukin-33 drives a proinflammatory endothelial activation that selectively targets nonquiescent cells. Arteriosclerosis, Thrombosis and Vascular Biology. ISSN 1079-5642. 33(2), s. e47–e55. doi: 10.1161/ATVBAHA.112.253427.
Sundlisæter, Eirik; Bekkeheien, Reidunn C; Hol, Johanna; Sponheim, Jon; Kuchler, Axel Matthias & Weiss, Miriam [Vis alle 10 forfattere av denne artikkelen] (2012). The Alarmin IL-33 Is a Notch Target in Quiescent Endothelial Cells. American Journal of Pathology. ISSN 0002-9440. 181(3), s. 1099–1111. doi: 10.1016/j.ajpath.2012.06.003.
Hol, Johanna; Otterdal, Kari; Breland, Unni Mathilde; Stang, Espen; Pedersen, Turid Margrethe & Hagelsteen, Kathrine [Vis alle 11 forfattere av denne artikkelen] (2012). Statins Affect the Presentation of Endothelial Chemokines by Targeting to Multivesicular Bodies. PLOS ONE. ISSN 1932-6203. 7(7). doi: 10.1371/journal.pone.0040673.
Pollheimer, Jürgen; Haslinger, Peter; Fock, Valerie; Prast, Johanna; Saleh, Leila & Biadasiewicz, Katarzyna [Vis alle 11 forfattere av denne artikkelen] (2011). Endostatin Suppresses IGF-II-Mediated Signaling and Invasion of Human Extravillous Trophoblasts. Endocrinology. ISSN 0013-7227. 152(11), s. 4431–4442. doi: 10.1210/en.2011-1196.
Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarstrøm, Clara Louise; Donaldson, Ian Matthew; Haraldsen, Guttorm & Bogen, Bjarne [Vis alle 7 forfattere av denne artikkelen] (2011). Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nature Communications. ISSN 2041-1723. 2. doi: 10.1038/ncomms1239.
Norrmén, C.; Vandevelde, Wouter; Ny, Annelii; Saharinen, Pipsa; Gentile, M. & Haraldsen, Guttorm [Vis alle 11 forfattere av denne artikkelen] (2010). Liprin beta 1 is highly expressed in lymphatic vasculature and is important for lymphatic vessel integrity. Blood. ISSN 0006-4971. 115(4), s. 906–909. doi: 10.1182/blood-2009-03-212274.
Sponheim, Jon; Pollheimer, Jürgen; Olsen, Trine; Balogh, Eva Johanna; Hammarström, Clara & Loos, Tamara [Vis alle 12 forfattere av denne artikkelen] (2010). Inflammatory Bowel Disease-Associated Interleukin-33 Is Preferentially Expressed in Ulceration-Associated Myofibroblasts. American Journal of Pathology. ISSN 0002-9440. 177(6), s. 2804–2815. doi: 10.2353/ajpath.2010.100378.
Mikalsen, Bjørg; Fosby, Bjarte; Wang, Jacob Edward; Hammarstrom, C; Brundvold, Hilde & Lundström, Marlene [Vis alle 10 forfattere av denne artikkelen] (2010). Genome-Wide Transcription Profile of Endothelial Cells After Cardiac Transplantation in the Rat. American Journal of Transplantation. ISSN 1600-6135. 10(7), s. 1534–1544. doi: 10.1111/j.1600-6143.2010.03157.x.
Hol, Johanna; Wilhelmsen, Linn & Haraldsen, Guttorm (2010). The murine IL-8 homologues KC, MIP-2, and LIX are found in endothelial cytoplasmic granules but not in Weibel-Palade bodies. Journal of Leukocyte Biology. ISSN 0741-5400. 87(3), s. 501–508. doi: 10.1189/jlb.0809532.
Haraldsen, Guttorm; Balogh, Eva Johanna; Pollheimer, Jürgen; Sponheim, Jon & Kuchler, Axel Matthias (2009). Interleukin-33-cytokine of dual function or novel alarmin? Trends in immunology. ISSN 1471-4906. 30(5), s. 227–233. doi: 10.1016/j.it.2009.03.003.
Hol, Johanna; Kuchler, Axel Matthias; Dalhus, Bjørn; Johansen, Finn Eirik; Haraldsen, Guttorm & Øynebråten, Inger (2009). Molecular Requirements for Sorting of the Chemokine Interleukin-8/CXCL8 to Endothelial Weibel-Palade Bodies. Journal of Biological Chemistry. ISSN 0021-9258. 284(35), s. 23532–23539. doi: 10.1074/jbc.M900874200.
Etokebe, Godfrey; Kuchler, Axel Matthias; Haraldsen, Guttorm; Landin, Maria Augusta Dos S Silva; Osmundsen, Harald & Dembic, Zlatko (2009). Family-with-sequence-similarity-46, member A (Fam46a) gene is expressed in developing tooth buds. Archives of Oral Biology. ISSN 0003-9969. 54(11), s. 1002–1007. doi: 10.1016/j.archoralbio.2009.08.005.
Sæthre, Marit; Schneider, MKJ; Lambris, JD; Magotti, P; Haraldsen, Guttorm & Seebach, JD [Vis alle 7 forfattere av denne artikkelen] (2008). Cytokine secretion depends on Gal alpha(1,3)Gal expression in a pig-to-human whole blood model. Journal of Immunology. ISSN 0022-1767. 180, s. 6346–6353.
Kuchler, Axel Matthias; Pollheimer, Jürgen; Balogh, Eva Johanna; Sponheim, Jon; Manley, Linda & Sørensen, Dag Reidar [Vis alle 9 forfattere av denne artikkelen] (2008). Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation. American Journal of Pathology. ISSN 0002-9440. 173, s. 1229–1242. doi: 10.2353/ajpath.2008.080014.
Breland, Unni Mathilde; Halvorsen, Bente ; Hol, Johanna; Øie, Erik; Paulsson-Berne, G & Yndestad, Arne [Vis alle 17 forfattere av denne artikkelen] (2008). A potential role of the CXC chemokine GRO alpha in atherosclerosis and plaque destabilization - Downregulatory effects of statins. Arteriosclerosis, Thrombosis and Vascular Biology. ISSN 1079-5642. 28. doi: 10.1161/ATVBAHA.108.162305.
Skovseth, Dag Kristian; Kuchler, Axel Matthias & Haraldsen, Guttorm (2007). The HUVEC/Matrigel assay: an in vivo assay of human angiogenesis suitable for drug validation. Methods in molecular biology. ISSN 1064-3745. 360, s. 253–268.
Sæthre, Marit; Lea, Tor; Borgen, Merethe S.; Fiane, Arnt E.; Michaelsen, Terje Einar & Thorsby, Erik [Vis alle 8 forfattere av denne artikkelen] (2006). Human complement-activating immunoglobulin (Ig)G3 antibodies are essential for porcine endothelial cell activation. Xenotransplantation. ISSN 0908-665X. 13(3), s. 215–223. doi: 10.1111/j.1399-3089.2006.00289x. Vis sammendrag
BACKGROUND: Complement-activating naturally occurring anti-porcine endothelial cell antibodies (Abs) are responsible for hyperacute rejection in porcine-to-primate transplantation, whereas the role of complement in acute vascular rejection, characterized by type II endothelial cell activation, is less well understood. We previously demonstrated a correlation between porcine type II endothelial cell activation, as detected by E-selectin expression, and human immunoglobulin (Ig)G3 anti-Gal alpha1-3Gal (Gal) Abs, which was not seen for IgG1, IgG2 or IgG4. The present study was undertaken to investigate whether there is a causal relationship between human anti-porcine IgG3 Abs and porcine endothelial cell activation. METHODS: IgG3 was isolated employing a Protein A column to 98.3% purity. Porcine endothelial cells were incubated with isolated human IgG3 or the combination of IgG1, IgG2 and IgG4. E-selectin expression and complement activation were investigated by flow cytometry and Western blotting, respectively. RESULTS: Purified IgG3, in contrast to the other IgG subclasses, induced a substantial increase in E-selectin expression. This activation was accompanied by complement activation as detected by C3 cleavage, and was abolished by heat inactivation or by adding the complement inhibitor FUT-175. Depletion of anti-Gal Abs reduced E-selectin expression by 60%, consistent with the presence of complement-activating anti-porcine non-Gal Abs of the IgG3 subclass. CONCLUSIONS: Collectively, these data strengthen the hypothesis that human anti-porcine endothelial cell Abs of the IgG3 subclass are essential for endothelial cell activation in porcine-to-human species grafts and demonstrate such activation to be partly independent of Gal epitopes.
Bækkevold, Espen Sønderaal; Wurbel, M-A; Kivisäkk, P; Wain, CM; Power, CA & Haraldsen, Guttorm [Vis alle 7 forfattere av denne artikkelen] (2005). A role for CCR4 in development of mature circulating cutaneous T helper memory cell populations. Journal of Experimental Medicine (JEM). ISSN 0022-1007. 201, s. 1045–1051.
Qiao, Shuo-Wang; Piper, J; Haraldsen, Guttorm; Øynebråten, Inger; Fleckenstein, Burkhard & Molberg, Øyvind [Vis alle 8 forfattere av denne artikkelen] (2005). Tissue transglutaminase-mediated formation and cleavage of histamine-gliadin complexes: biological effects and implications for celiac disease. Journal of Immunology. ISSN 0022-1767. 174, s. 1657–1663.
Skovseth, Dag Kristian; Veuger, Maria Johanna; Sørensen, Dag Reidar; De Angelis, Paula & Haraldsen, Guttorm (2005). Endostatin dramatically inhibits endothelial cell migration, vascular morphogenesis and perivascular cell recruitment in vivo. Blood. ISSN 0006-4971. 105, s. 1044–1051.
Corthay, Alexandre; Skovseth, Dag Kristian; Lundin, Katrin; Røsjø, Egil; Omholt, Hilde & Hofgaard, Peter Olaf [Vis alle 8 forfattere av denne artikkelen] (2005). Primary antitumor immune response mediated by CD4+ T cells. Immunity. ISSN 1074-7613. 22, s. 371–383.
Carlsen, Hege Synnøve; Haraldsen, Guttorm; Brandtzæg, Per & Bækkevold, Espen Sønderaal (2005). Disparate lymphoid chemokine expression in mice and men: no evidence of CCL21 synthesis by human high endothelial venules. Blood. ISSN 0006-4971. 106, s. 444–446.
Øynebråten, Inger; Barois, Nicolas; Hagelsteen, Kathrine; Johansen, Finn Eirik; Bakke, Oddmund & Haraldsen, Guttorm (2005). Characterization of a novel chemokine-containing storage granule in endothelial cells: evidence for preferential exocytosis mediated by protein kinase A and diacylglycerol. Journal of Immunology. ISSN 0022-1767. 175(8), s. 5358–5369. Vis sammendrag
We have recently shown that several proinflammatory chemokines can be stored in secretory granules of endothelial cells (ECs). Subsequent regulated exocytosis of such chemokines may then enable rapid recruitment of leukocytes to inflammatory sites. Although IL-8/CXCL8 and eotaxin-3/CCL26 are sorted to the rod-shaped Weibel-Palade body (WPB), we found that GROalpha/CXCL1 and MCP-1/CCL2 reside in small granules that, similarly to the WPB, respond to secretagogue stimuli. In the present study, we report that GROalpha and MCP-1 colocalized in 50- to 100-nm granules, which occur throughout the cytoplasm and at the cell cortex. Immunofluorescence confocal microscopy revealed no colocalization with multimerin or tissue plasminogen activator, i.e., proteins that are released from small granules of ECs by regulated exocytosis. Moreover, the GROalpha/MCP-1-containing granules were Rab27-negative, contrasting the Rab27-positive, WPB. The secretagogues PMA, histamine, and forskolin triggered distinct dose and time-dependent responses of GROalpha release. Furthermore, GROalpha release was more sensitive than IL-8 release to inhibitors and activators of PKA and PKC but not to an activator of Epac, a cAMP-regulated GTPase exchange factor, indicating that GROalpha release is regulated by molecular adaptors different from those regulating exocytosis of the WPB. On the basis of these findings, we designated the GROalpha/MCP-1-containing compartment the type 2 granule of regulated secretion in ECs, considering the WPB the type 1 compartment. In conclusion, we propose that the GROalpha/MCP-1-containing type 2 granule shows preferential responsiveness to important mediators of EC activation, pointing to the existence of selective agonists that would allow differential release of selected chemokines.
Øynebråten, Inger; Barois, Nicolas; Hagelsteen, Kathrine; Johansen, Finn Eirik; Bakke, Oddmund & Haraldsen, Guttorm (2005). Characterization of a novel chemokine-containing storage granule in endothelial cells: evidence for preferential exocytosis mediated by protein kinase A and diacylglycerol. Journal of Immunology. ISSN 0022-1767. 175(8), s. 5358–5369. Vis sammendrag
We have recently shown that several proinflammatory chemokines can be stored in secretory granules of endothelial cells (ECs). Subsequent regulated exocytosis of such chemokines may then enable rapid recruitment of leukocytes to inflammatory sites. Although IL-8/CXCL8 and eotaxin-3/CCL26 are sorted to the rod-shaped Weibel-Palade body (WPB), we found that GROalpha/CXCL1 and MCP-1/CCL2 reside in small granules that, similarly to the WPB, respond to secretagogue stimuli. In the present study, we report that GROalpha and MCP-1 colocalized in 50- to 100-nm granules, which occur throughout the cytoplasm and at the cell cortex. Immunofluorescence confocal microscopy revealed no colocalization with multimerin or tissue plasminogen activator, i.e., proteins that are released from small granules of ECs by regulated exocytosis. Moreover, the GROalpha/MCP-1-containing granules were Rab27-negative, contrasting the Rab27-positive, WPB. The secretagogues PMA, histamine, and forskolin triggered distinct dose and time-dependent responses of GROalpha release. Furthermore, GROalpha release was more sensitive than IL-8 release to inhibitors and activators of PKA and PKC but not to an activator of Epac, a cAMP-regulated GTPase exchange factor, indicating that GROalpha release is regulated by molecular adaptors different from those regulating exocytosis of the WPB. On the basis of these findings, we designated the GROalpha/MCP-1-containing compartment the type 2 granule of regulated secretion in ECs, considering the WPB the type 1 compartment. In conclusion, we propose that the GROalpha/MCP-1-containing type 2 granule shows preferential responsiveness to important mediators of EC activation, pointing to the existence of selective agonists that would allow differential release of selected chemokines.
Fiane, Arnt E; Ueland, Thor; Simonsen, Svein; Scott, Helge; Endresen, Knut & Gullestad, Lars [Vis alle 14 forfattere av denne artikkelen] (2005). Low mannose-binding lectin and increased complement activation correlate to allograft vasculopathy, ischaemia, and rejection after human heart transplantation. European Heart Journal. ISSN 0195-668X. 26(16), s. 1660–1665.
Øynebråten, Inger; Oynebraten, Inger; Bakke, Oddmund; Brandtzæg, Per; Johansen, Finn Erik & Haraldsen, Guttorm (2004). Rapid chemokine secretion from endothelial cells originates from 2 distinct compartments. Blood. ISSN 0006-4971. 104(2), s. 314–320. Vis sammendrag
The neutrophil-attracting chemokine interleukin 8 (IL-8) is stored in the Weibel-Palade body (WPB) of endothelial cells (ECs) from which it can be rapidly released after exposure to the secretagogues histamine or thrombin. In this manner, IL-8 may enable rapid recruitment of leukocytes to inflammatory sites. To explore the possible storage of EC-derived chemokines that may attract other subsets of leukocytes, we examined the intracellular localization and secretagogue responsiveness of growth-related oncogene alpha (GROalpha), monocyte chemoattractant protein-1 (MCP-1), eotaxin-3, interferon-gamma-inducible protein 10 (IP-10), and regulated on activation, normal T-cell expressed and secreted (RANTES). While eotaxin-3, GROalpha, and MCP-1 were rapidly released from ECs, the release of the T-cell attractors RANTES and IP-10 was not sensitive to the secretagogues. Moreover, of the 3 former chemokines, only eotaxin-3 was stored in WPBs. GROalpha and MCP-1 resided mainly in smaller vesicles compatible with sorting to a different, histamine-responsive compartment, which has been described in ECs although not reported to contain chemokines. In conclusion, we propose that rapid release of chemokines is restricted to those primarily recruiting leukocytes of the innate immune system, and that their storage in ECs is not restricted to the WPB compartment.
Lacorre, D-A; Bækkevold, Espen S.; Garrido, I; Brandtzæg, Per; Haraldsen, Guttorm & Amalric, F [Vis alle 7 forfattere av denne artikkelen] (2004). Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated high endothelial venule endothelial cells outside the lymphoid tissue microenvironment. Blood. ISSN 0006-4971. 103, s. 4164–4172.
Bækkevold, Espen S.; Roussigné, M; Yamanaka, Takeshi; Johansen, Finn Eirik; Jahnsen, Frode Lars & Amalric, F [Vis alle 10 forfattere av denne artikkelen] (2003). Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules. American Journal of Pathology. ISSN 0002-9440. 163, s. 69–79.
Chi, J-T; Chang, HY; Haraldsen, Guttorm; Jahnsen, Frode Lars; Troyanskaya, OG & Chang, DS [Vis alle 11 forfattere av denne artikkelen] (2003). Endothelial cell diversity revealed by global expression profiling. Proceedings of the National Academy of Sciences of the United States of America. ISSN 0027-8424. 100, s. 10623–10628.
Carlsen, Hege Synnøve; Bækkevold, Espen S.; Johansen, Finn Eirik; Haraldsen, Guttorm & Brandtzæg, Per (2002). B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue. Gut. ISSN 0017-5749. 51, s. 364–371.
Farstad, Inger Nina; Malavasi, F.; Haraldsen, Guttorm; Huitfeldt, Henrik & Brandtzæg, Per (2002). CD38 is a marker of human lacteals. Virchows Archiv. ISSN 0945-6317. 441, s. 605–613.
Skovseth, Dag Kristian; Yamamoto, Takeshi; Brandtzæg, Per; Butcher, Eugene & Haraldsen, Guttorm (2002). Vascular morphogenesis and differentiation following adoptive transfer of human endothelial cells to immunodeficient mice. American Journal of Pathology. ISSN 0002-9440. 160, s. 1629–1637.
Skovseth, Dag Kristian; Sørensen, Dag R. & Haraldsen, Guttorm (2002). Vascular morphogenesis and differentiation following adoptive transfer of human endothelial cells to immunodeficient mice. American Journal of Pathology. ISSN 0002-9440.
Sæthre, Marit; Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva & Thorsby, Erik [Vis alle 8 forfattere av denne artikkelen] (2002). Human serum-induced porcine endothelial cell E-selectin expression is associated with IgG3 and IgM anti-Gal antibodies. Xenotransplantation. ISSN 0908-665X. 9, s. 350–358.
Bækkevold, Espen S.; Yamamoto, Takeshi; Palframan, R.T.; Carlsen, Hege Synnøve; Reinholt, Finn P. & Andrian, U. H. von [Vis alle 8 forfattere av denne artikkelen] (2001). The CCR7 ligand ELC (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. Journal of Experimental Medicine (JEM). ISSN 0022-1007. 193(9), s. 1105–1112. Vis sammendrag
Lymphocyte homing to secondary lymphoid tissue is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial selectin-mediated tethering and rolling, firm adhesion of lymphocytes requires rapid upregulation of lymphocyte integrin adhesiveness. This step is mediated in part by the HEV-derived chemokine SLC (secondary lymphoid-tissue chemokine, or CCL21) that binds to the CC chemokine receptor (CCR)7 on lymphocytes. However, the CC chemokine ELC (Epstein-Barr virus-induced molecule 1 ligand chemokine, or CCL19) shares the same receptor, and ELC transcripts have been observed in the T cell areas of lymphoid organs. Here, we show that perivascular ELC is transcytosed to the luminal surfaces of HEVs and enables efficient T cell homing to lymph nodes. In situ hybridization on sections of human tonsil showed no ELC mRNA in HEVs, but immunostaining revealed ELC protein in cytoplasmic vesicles of HEV cells. Furthermore, ELC injected into the footpads of mice entered the draining lymph nodes and was presented by HEVs. Finally, intracutaneous injections of ELC in mice lacking functionally relevant ELC and SLC (plt/plt mice) restored T cell trafficking to draining lymph nodes as efficiently as SLC. We conclude that perivascular ELC is transcytosed to the luminal surfaces of HEVs and participates in CCR7-mediated triggering of lymphocyte arrest.
Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva; Lambris, J.D. & Fung, M. [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced E-selectin expression on porcine aortic endothelial cells in vitro is totally complement mediated. Transplantation. ISSN 0041-1337. 72, s. 1967–1973. Vis sammendrag
Abstract: Background. Whereas complement is a key mediator of hyperacute xenograft rejection, its role in acute vascular rejection (AVR) is a matter of controversy. AVR is associated with de novo synthesis of endothelial cell-derived inflammatory mediators, including the leukocyte-recruiting adhesion molecule E-selectin. Here we investigate the role and mechanism of complement in human serum-induced porcine endothelial cell activation. Methods. An in vitro xenotransplantation method was designed using porcine aortic endothelial cells stimulated with human serum in micro-culture wells. E-selectin expression was measured by cell-enzyme immunoassay. Complement inhibitors acting at different levels in the cascade were investigated for their effect on E-selectin expression. Results. E-selectin was strongly induced by normal human serum, but not by heat-inactivated serum. Compstatin, a synthetic C3 inhibitor, markedly reduced human serum-induced E-selectin expression. Purified C1-inhibitor suppressed E-selectin induction completely, indicating activation through the classical or lectin pathway. Furthermore, a mAb that inhibits cleavage of C5 or another mAb that blocks the function of C7, completely inhibited the expression of serum-induced E-selectin, consistent with the terminal C5b-9 complement complex being the mediator of the endothelial cell activation. Inhibition of the alternative pathway using a novel anti-factor D mAb did not reduce E-selectin expression. Conclusion. Human serum-induced expression of porcine E-selectin is totally complement dependent, induced by a C1-inhibitor regulated pathway, and mediated through the terminal complement complex. The data may have implications for therapeutic strategies, particularly of C1-inhibitor and anti-C5 mAb, to protect against endothelial cell activation and subsequent AVR of porcine xenografts. Abstract: Background. Whereas complement is a key mediator of hyperacute xenograft rejection, its role in acute vascular rejection (AVR) is a matter of controversy. AVR is associated with de novo synthesis of endothelial cell-derived inflammatory mediators, including the leukocyte-recruiting adhesion molecule E-selectin. Here we investigate the role and mechanism of complement in human serum-induced porcine endothelial cell activation. Methods. An in vitro xenotransplantation method was designed using porcine aortic endothelial cells stimulated with human serum in micro-culture wells. E-selectin expression was measured by cell-enzyme immunoassay. Complement inhibitors acting at different levels in the cascade were investigated for their effect on E-selectin expression. Results. E-selectin was strongly induced by normal human serum, but not by heat-inactivated serum. Compstatin, a synthetic C3 inhibitor, markedly reduced human serum-induced E-selectin expression. Purified C1-inhibitor suppressed E-selectin induction completely, indicating activation through the classical or lectin pathway. Furthermore, a mAb that inhibits cleavage of C5 or another mAb that blocks the function of C7, completely inhibited the expression of serum-induced E-selectin, consistent with the terminal C5b-9 complement complex being the mediator of the endothelial cell activation. Inhibition of the alternative pathway using a novel anti-factor D mAb did not reduce E-selectin expression. Conclusion. Human serum-induced expression of porcine E-selectin is totally complement dependent, induced by a C1-inhibitor regulated pathway, and mediated through the terminal complement complex. The data may have implications for therapeutic strategies, particularly of C1-inhibitor and anti-C5 mAb, to protect against endothelial cell activation and subsequent AVR of porcine xenografts. Abstract: Background. Whereas complement is a key mediator of hyperacute xenograft rejection, its role in acute vascular rejection (AVR) is a matter of controversy. AVR is associated with de n...
Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva; Thorsby, Erik & Mollnes, Tom Eirik (2001). C1-inhibitor attenuates human serum induced E-selectin expression of pig aortic endothelial cells. Transplantation Proceedings. ISSN 0041-1345. 33, s. 789–790. Vis sammendrag
Abstract ikke tilgjengelig.
Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva; Lambris, J.D. & Fung, M. [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced E-selectin expression on porcine aortic endothelial cells in vitro is totally complement mediated. Transplantation. ISSN 0041-1337. 72, s. 1967–1973. Vis sammendrag
Abstract: Background. Whereas complement is a key mediator of hyperacute xenograft rejection, its role in acute vascular rejection (AVR) is a matter of controversy. AVR is associated with de novo synthesis of endothelial cell-derived inflammatory mediators, including the leukocyte-recruiting adhesion molecule E-selectin. Here we investigate the role and mechanism of complement in human serum-induced porcine endothelial cell activation. Methods. An in vitro xenotransplantation method was designed using porcine aortic endothelial cells stimulated with human serum in micro-culture wells. E-selectin expression was measured by cell-enzyme immunoassay. Complement inhibitors acting at different levels in the cascade were investigated for their effect on E-selectin expression. Results. E-selectin was strongly induced by normal human serum, but not by heat-inactivated serum. Compstatin, a synthetic C3 inhibitor, markedly reduced human serum-induced E-selectin expression. Purified C1-inhibitor suppressed E-selectin induction completely, indicating activation through the classical or lectin pathway. Furthermore, a mAb that inhibits cleavage of C5 or another mAb that blocks the function of C7, completely inhibited the expression of serum-induced E-selectin, consistent with the terminal C5b-9 complement complex being the mediator of the endothelial cell activation. Inhibition of the alternative pathway using a novel anti-factor D mAb did not reduce E-selectin expression. Conclusion. Human serum-induced expression of porcine E-selectin is totally complement dependent, induced by a C1-inhibitor regulated pathway, and mediated through the terminal complement complex. The data may have implications for therapeutic strategies, particularly of C1-inhibitor and anti-C5 mAb, to protect against endothelial cell activation and subsequent AVR of porcine xenografts.
Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva; Thorsby, Erik & Mollnes, Tom Eirik (2001). C1 inhibitor attenuates human serum induced E-selectin expression of pig aortic endothelial cells. Transplantation Proceedings. ISSN 0041-1345. s. 789–790.
Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva; Lambris, J.D. & Fung, M. [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced E-selectin expression on porcine aortic endothelial cells in vitro is totally complement mediated. Transplantation. ISSN 0041-1337.
Kunkel, Eric; Campbell, James; Haraldsen, Guttorm; Pan, Junliang; Boisvert, Judie & Roberts, Arthur [Vis alle 16 forfattere av denne artikkelen] (2000). Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. Journal of Experimental Medicine (JEM). ISSN 0022-1007. s. 761–767.
Sindre, Hilde; Haraldsen, Guttorm; Beck, Solveig; Hestad, Kjetil; Kvale, Dag & Brandtzæg, Per [Vis alle 8 forfattere av denne artikkelen] (2000). Human intestinal endothelium shows high susceptibility to cytomegalovirus and altered expression of adhesion molecules after infection. Scandinavian Journal of Immunology. ISSN 0300-9475. 51, s. 354–360.

Se alle arbeider i Cristin

Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarström, Clara Louise; Donaldson, Ian M; Haraldsen, Guttorm & Bogen, Bjarne [Vis alle 7 forfattere av denne artikkelen] (2016). Kreft-spesifikke betennelsesreaksjoner kan beskytte mot kreft. BestPractice. Onkologi Hematologi. February.
Schjesvold, Fredrik Hellem; Tveita, Anders; Sundnes, Olav; Haraldsen, Guttorm & Bogen, Bjarne (2013). CD4+T cell-mediated protection against tumors: no bystander killing. Journal of Immunology. ISSN 0022-1767. 190.
Haraldsen, Guttorm (2013). Interleukin-33 drives a proinflammatory endothelial activation that selectively targets non-quiescent cells. The FASEB Journal. ISSN 0892-6638. 27.
Sundnes, Olav; Khnykin, Denis & Haraldsen, Guttorm (2013). Cellular expression of the alarmin IL-33 in acute skin inflammation. Journal of Investigative Dermatology. ISSN 0022-202X. 133, s. S52–S52.
Haraldsen, Guttorm; Jetne, Reidunn; Hol, Johanna; Sponheim, Jon; Kuchler, Axel Matthias & Kasprzycka, Monika [Vis alle 7 forfattere av denne artikkelen] (2012). The Alarmin Interleukin-33 is a Notch Target in Quiescent Endothelial Cells. Journal of Immunology. ISSN 0022-1767. 188.
Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarström, Clara; Donaldson, Ian Matthew; Haraldsen, Guttorm & Bogen, Bjarne [Vis alle 7 forfattere av denne artikkelen] (2011). Cancer Immunosurveillance by CD4(+) T Cells. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(6), s. 603–603.
Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarstrom, C; Donaldson, Ian Matthew; Haraldsen, Guttorm & Bogen, Bjarne [Vis alle 7 forfattere av denne artikkelen] (2011). A cancer-protective role of inflammation. Cytokine. ISSN 1043-4666. 56(1), s. 101–101. doi: 10.1016/j.cyto.2011.07.392.
Sundlisæter, Eirik; Bekkeheien, Reidunn C; Hol, Johanna; Sponheim, Jon; Kuchler, Axel Matthias & Kasprzycka, Monika [Vis alle 7 forfattere av denne artikkelen] (2011). The Putative Alarmin IL-33 is Induced and Maintained in Resting Endothelial Cells by Notch Ligand DLL4. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), s. 366–366.
Haabeth, Ole Audun; Lorvik, Kristina Berg; Hammarström, Clara; Donaldson, Ian Matthew; Haraldsen, Guttorm & Bogen, Bjarne [Vis alle 7 forfattere av denne artikkelen] (2011). Inflammation Driven by Tumor-Specific Th1 Cells Protects against B-Cell Cancer. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), s. 384–384.
Sponheim, Jon; Pollheimer, Jürgen; Olsen, Trine; Balogh, Johanna; Hammarström, Clara & Loos, Tamara [Vis alle 12 forfattere av denne artikkelen] (2010). Inflammatory bowel disease-associated interleukin-33 is preferentially expressed in ulceration-associated myofibroblasts. Wound Repair and Regeneration. ISSN 1067-1927. 18(6), s. A94–A94.
Hol, Johanna; Kuchler, Axel Matthias; Johansen, Finn Eirik; Haraldsen, Guttorm & Øynebråten, Inger (2008). Molecular requirements for sorting of IL-8/CXCL8 to endothelial Weibel Palade bodies. Scandinavian Journal of Immunology. ISSN 0300-9475. 68, s. 228–229.
Mikalsen, Bjørg; Lundström, Marlene; Fosby, Bjarte; Hammarstrom, C; Bjaerke, H & Wang, J [Vis alle 10 forfattere av denne artikkelen] (2008). Genome-wide transcription profiles of endothelial cells during cardiac allograft rejection. Scandinavian Journal of Immunology. ISSN 0300-9475. 68, s. 220–221.
Josefsen, Dag; Kuechler, A; Wang, Mari; Haraldsen, Guttorm & Kvalheim, Gunnar (2008). Human bone marrow mononuclear cells, CD34+cells and CD133+cells do not form vascular structures in vivo. Bone Marrow Transplantation. ISSN 0268-3369. 41, s. S130–S130.
Westgaard, Arne; Carlsen, Hege Synnøve; Bækkevold, Espen S.; Haraldsen, Guttorm; Bergan, Anstein Bjørnar & Brandtzæg, Per (2002). "B-cell attracting chemokine 1" (CXCL13): Mulig patogenetisk rolle i inflammatorisk tarmsykdom? Vis sammendrag
B-CELL ATTRACTING CHEMOKINE 1 (CXCL13): MULIG PATOGENETISK ROLLE I INFLAMMATORISK TARMSYKDOM? Kjemokiner er samlebetegnelse for en gruppe peptider som virker som kjemoattraktanter for leukocytter. De siste årene har flere kjemokiner blitt karakterisert, og det er vist at de spiller en avgjørende rolle for trafikkering av lymfocytter. Studier i dyremodeller har vist at �B-cell attracting chemokine-1� (CXCL13) er tilstrekkelig for å indusere forandringer som fører til dannelse av organisert lymfoid vev, og reseptoren for dette kjemokinet, CXCR5, er nødvendig for normal utvikling av sekundært lymfoid vev. Studier av humant vev har påvist CXCL13 i ventrikkel og appendiks, men ikke i andre deler av normal eller syk tarm hos menneske. Vi har derfor studert ekspresjonen av dette kjemokinet og dets reseptor i tarmens normale lymfoide vev og lesjoner av ulcerøs kolitt. MATERIALE OG METODER: Frysesnitt fra kirurgiske preparater ble studert med dobbel og trippel immunfluoresens-farging, in situ mRNA-hybridisering og polymerase-kjedereaksjon (RT-PCR) . RESULTATER: Vi fant CXCL13-mRNA i alle preparater fra normal kolon og ulcerøs kolitt. CXCL13 var delvis assosiert med folikkulære dendrittiske celler, men også med ekstracellulære fibriller både i tarmens normale lymfoide vev og i irregulære lymfoide aggregater i lesjoner av ulcerøs kolitt. I betent vev fant vi også CXCL13- produserende celler i små ansamlinger av B-celler. CXCR5-protein ble detektert på B-celler i mantelsonen og på spredte T-celler i folikkulære kimsentre. Vi fant CXCR5 i alle lymfoide aggregater både i frisk og syk tarm. KONKLUSJONER: Kjemokinet CXCL13 og dets reseptor CXCR5 er uttrykt i tarmens normale lymfoide vev og også i irregulære lymfoide aggregater i ulcerøs kolitt. Funnet tyder på at dette kjemokinet spiller en viktig rolle, ikke bare for utviklingen av tarmens normale lymfoide vev, men også for dannelsen av irregulære lymfoide aggregater i ulcerøs kolitt. Hvordan, og i hvilken grad, dannelsen av irregulære lymfoide aggregater påvirker utvikling og opprettholdelse av sykdom er imidlertid uklart, og videre studier er nødvendig.
Sæthre, Marit; Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva & Thorsby, Erik [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced porcine endothelial cell E-selectin expression is associated with IgG3 anti-Gal antibodies.
Bækkevold, Espen S.; Yamamoto, Takeshi; Palframan, R.T.; Carlsen, Hege Synnøve; Reinholt, Finn P. & Andrian, U. H. von [Vis alle 8 forfattere av denne artikkelen] (2001). The CCR7-ligand ELC (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment.
Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva; Lambris, J.D. & Fung, M. [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced E-selectin expression on porcine aortic endothelial cells is totally complement mediated: Evidence for a role of complement in delayed xenograft rejection.
Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva; Lambris, J.D. & Fung, M. [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced E-selectin expression on porcine aortic endothelial cells is totally complement mediated: evidence for a role of complement in delayed xenograft rejection.
Sæthre, Marit; Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva & Thorsby, Erik [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced porcine endothelial cell E-selectin expression is associated with Ig3 anti-gal antibodies.
Bækkevold, Espen S.; Yamamoto, Takeshi; Carlsen, Hege Synnøve; Brandtzæg, Per & Haraldsen, Guttorm (2001). Transcytosis of the CC chemokine ELC/CCL19 in human high endothelial venules.
Sæthre, Marit; Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva & Thorsby, Erik [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced porcine endothelial cell E-selectin expression is associated with IgG3 anti-Gal antibodies. Vis sammendrag
Abstract ikke tilgjenelig.
Sæthre, Marit; Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva & Thorsby, Erik [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced porcine endothelial cell E-selectin expression is associated with IgG3 anti-Gal antibodies. Vis sammendrag
Blodtapping er fortsatt vanlig behandling for sykdommer som hemokromatose og polycytemi. I 1999 ble ca. 5 900 terapeutiske blodtappinger utført ved norske blodbanker. Både pasienter og helsepersonell ønsker at blodet som tappes skal komme til nytte, fortrinnsvis ved at blodbankene aksepterer at disse pasientene kan være blodgivere. Vi undersøkte henvisningsbrevet til alle pasienter som ble tappet terapeutisk i en 12-månedersperiode, ved to sykehus, for å se hvor ofte brevet gav informasjon som ville utelukke at pasienten kunne være blodgiver. Til sammen ble det tappet 1 116 enheter blod fra 177 pasienter. 122 pasienter som ble tappet 696 ganger, hadde informasjon i henvisningsbrevet som ville utelukke vanlig blodgivning. De resterende 55 pasientene kunne ha vært undersøkt videre for å se om de hadde fylt kravene til blodgivere. Noen pasienter som trenger blodtapping kan medisinsk sett være blodgivere, men langt fra alle. I tillegg skal blodgiving være frivillig og ubetalt, og motivet skal være uegennyttig. Dette vil ikke være tilfellet for blodgivere med sykdommer der behandlingen nettopp er blodgiving. Nødvendige tiltak for å kompensere for dette diskuteres.
Sølvik, Una Ørvim; Haraldsen, Guttorm; Fiane, Arnt E.; Boretti, Eva; Lambris, J.D. & Fung, M. [Vis alle 8 forfattere av denne artikkelen] (2001). Human serum-induced E-selectin expression on porcine aortic endothelial cells is totally complement mediated: Evidence for a role of complement in delayed xenograft rejection.
Sponheim, Jon; Haraldsen, Guttorm; Vatn, Morten H & Torsvik, Harald (2012). Inerleukin-33 in inflammation and wound repair : an experimental study with special reference to endothelial cells and myofibroblats. Unipub forlag. ISSN 978-82-8264-358-0. 2012(1329).
Mikalsen, Bjørg & Haraldsen, Guttorm (2011). Genome-wide endothelial cell activation profiles and matricellular protein expression after solid organ transplantation. Unipub forlag. ISSN 978-82-8072-558-5.
Hol, Johanna & Haraldsen, Guttorm (2010). Sorting, storage and secretion of neutrophil-recruiting CXC chemokines from endothelial cells. Unipub forlag. ISSN 978-82-8072-367-3.

Se alle arbeider i Cristin

Publisert 13. apr. 2011 11:46 - Sist endret 5. jan. 2024 12:47

Forskergrupper

Inflammasjon og vaskulær biologi