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Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
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2005 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 54, no 6, 1755-62 p.Article in journal (Refereed) Published
Abstract [en]

There are strong indications that only a small fraction of grafts successfully engraft in clinical islet transplantation. One explanation may be the instant blood-mediated inflammatory reaction (IBMIR) elicited by tissue factor, which is produced by the endocrine cells. In the present study, we show that islets intended for islet transplantation produce tissue factor in both the transmembrane and the alternatively spliced form and that the membrane-bound form is released as microparticles often associated with both insulin and glucagon granules. A low-molecular mass factor VIIa (FVIIa) inhibitor that indirectly blocks both forms of tissue factor was shown in vitro to be a promising drug to eliminate the IBMIR. Thrombin-antithrombin complex (TAT) and FVIIa-antithrombin complex (FVIIa-AT) were measured in nine patients who together received 20 infusions of isolated human islets. Both the TAT and FVIIa-AT complexes increased rapidly within 15-60 min after infusion. When the initial TAT and FVIIa-AT levels were plotted against the increase in C-peptide concentration after 7 days, patients with an initially strong IBMIR showed no significant increase in insulin synthesis after 7 days. In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets.

Place, publisher, year, edition, pages
2005. Vol. 54, no 6, 1755-62 p.
Keyword [en]
Adult, Alternative Splicing/physiology, Antithrombin III/physiology, Factor VIIa/antagonists & inhibitors/physiology, Female, Humans, Immunohistochemistry, Inflammation/physiopathology, Islets of Langerhans/*physiology/ultrastructure, Islets of Langerhans Transplantation, Male, Middle Aged, Peptide Hydrolases/physiology, Thromboplastin/*physiology, Time Factors
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-25571DOI: 10.2337/diabetes.54.6.1755PubMedID: 15919797OAI: oai:DiVA.org:uu-25571DiVA: diva2:53345
Available from: 2008-08-01 Created: 2008-08-01 Last updated: 2017-12-07Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=15919797&dopt=Citation

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Johansson, HelenaLukinius, AgnetaMoberg, LisaBerne, ChristianTufveson, GunnarEkdahl, Kristina NilssonElgue, GracielaKorsgren, OlleNilsson, Bo

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Johansson, HelenaLukinius, AgnetaMoberg, LisaBerne, ChristianTufveson, GunnarEkdahl, Kristina NilssonElgue, GracielaKorsgren, OlleNilsson, Bo
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Department of Oncology, Radiology and Clinical ImmunologyDepartment of Genetics and PathologyDepartment of Surgical SciencesTransplantation Surgery
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