HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Özmen, L. Articles by Nilsson, B. Search for Related Content PubMed PubMed Citation Articles by Özmen, L. Articles by Nilsson, B. Social Bookmarking                What's this?

Inhibition of Thrombin Abrogates the Instant Blood-Mediated Inflammatory Reaction Triggered by Isolated Human Islets

Possible Application of the Thrombin Inhibitor Melagatran in Clinical Islet Transplantation

¹ Department of Radiology, Oncology and Clinical Immunology, Division of Clinical Immunology, the Rudbeck Laboratory, University Hospital, Uppsala, Sweden
² Department of Chemistry and Biomedical Science, University of Kalmar, Kalmar, Sweden

A thrombotic/inflammatory reaction is elicited when isolated islets of Langerhans come in contact with ABO-compatible blood. The detrimental effects of this instant blood-mediated inflammatory reaction (IBMIR) provide a reasonable explanation for the observation that an unexpectedly high number of islets, from several donors, are needed to produce normoglycemia in transplant patients with type 1 diabetes. In this study, the hypothesis that a specific thrombin inhibitor, Melagatran, could reduce IBMIR in an in vitro model in which human islets are exposed to ABO-compatible blood was tested. The administration of Melagatran abrogated IBMIR dose-dependently. Islets exposed to blood, in the absence or presence of 0.4 µmol/l Melagatran, exhibited a loss of integrity and were found to be trapped in macroscopic clots containing platelets and CD11b⁺ leukocytes. At concentrations from 1 to 10 µmol/l, Melagatran inhibited both coagulation and complement activation. Also, platelet and leukocyte activation and consumption were decreased. Islet morphology was maintained with almost no platelets adhering to the surface, and infiltration by CD11b⁺ leukocytes was considerably reduced. In conclusion, Melagatran significantly reduced IBMIR in this model system. This protective effect indicates that thrombin plays a pivotal role in IBMIR and suggests that thrombin inhibition can improve the outcome of clinical islet transplantation.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. A. Emamaullee, J. Davis, R. Pawlick, C. Toso, S. Merani, S.-X. Cai, B. Tseng, and A.M. J. Shapiro The Caspase Selective Inhibitor EP1013 Augments Human Islet Graft Function and Longevity in Marginal Mass Islet Transplantation in Mice Diabetes, June 1, 2008; 57(6): 1556 - 1566. [Abstract] [Full Text] [PDF]

				D. Su, N. Zhang, J. He, S. Qu, S. Slusher, R. Bottino, S. Bertera, J. Bromberg, and H. H. Dong Angiopoietin-1 Production in Islets Improves Islet Engraftment and Protects Islets From Cytokine-Induced Apoptosis Diabetes, September 1, 2007; 56(9): 2274 - 2283. [Abstract] [Full Text] [PDF]

				S. Cabric, J. Sanchez, T. Lundgren, A. Foss, M. Felldin, R. Kallen, K. Salmela, A. Tibell, G. Tufveson, R. Larsson, et al. Islet Surface Heparinization Prevents the Instant Blood-Mediated Inflammatory Reaction in Islet Transplantation Diabetes, August 1, 2007; 56(8): 2008 - 2015. [Abstract] [Full Text] [PDF]

				J. A. Emamaullee, L. Stanton, C. Schur, and A.M. J. Shapiro Caspase Inhibitor Therapy Enhances Marginal Mass Islet Graft Survival and Preserves Long-Term Function in Islet Transplantation Diabetes, May 1, 2007; 56(5): 1289 - 1298. [Abstract] [Full Text] [PDF]

				R. Lehmann, R. A. Zuellig, P. Kugelmeier, P. B. Baenninger, W. Moritz, A. Perren, P.-A. Clavien, M. Weber, and G. A. Spinas Superiority of Small Islets in Human Islet Transplantation Diabetes, March 1, 2007; 56(3): 594 - 603. [Abstract] [Full Text] [PDF]

				J. A. Emamaullee and A.M. J. Shapiro Interventional Strategies to Prevent {beta}-Cell Apoptosis in Islet Transplantation. Diabetes, July 1, 2006; 55(7): 1907 - 1914. [Abstract] [Full Text] [PDF]

				H. Johansson, A. Lukinius, L. Moberg, T. Lundgren, C. Berne, A. Foss, M. Felldin, R. Kallen, K. Salmela, A. Tibell, et al. Tissue Factor Produced by the Endocrine Cells of the Islets of Langerhans Is Associated With a Negative Outcome of Clinical Islet Transplantation Diabetes, June 1, 2005; 54(6): 1755 - 1762. [Abstract] [Full Text] [PDF]

				N. R. Barshes, S. Wyllie, and J. A. Goss Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts J. Leukoc. Biol., May 1, 2005; 77(5): 587 - 597. [Abstract] [Full Text] [PDF]

				J. L. Contreras, C. Eckstein, C. A. Smyth, G. Bilbao, M. Vilatoba, S. E. Ringland, C. Young, J. A. Thompson, J. A. Fernandez, J. H. Griffin, et al. Activated Protein C Preserves Functional Islet Mass After Intraportal Transplantation: A Novel Link Between Endothelial Cell Activation, Thrombosis, Inflammation, and Islet Cell Death Diabetes, November 1, 2004; 53(11): 2804 - 2814. [Abstract] [Full Text] [PDF]

				C. Beuneu, O. Vosters, B. Movahedi, M. Remmelink, I. Salmon, D. Pipeleers, O. Pradier, M. Goldman, and V. Verhasselt Human Pancreatic Duct Cells Exert Tissue Factor-Dependent Procoagulant Activity: Relevance to Islet Transplantation Diabetes, June 1, 2004; 53(6): 1407 - 1411. [Abstract] [Full Text] [PDF]

				R. Gao, J. Ustinov, M.-A. Pulkkinen, K. Lundin, O. Korsgren, and T. Otonkoski Characterization of Endocrine Progenitor Cells and Critical Factors for Their Differentiation in Human Adult Pancreatic Cell Culture Diabetes, August 1, 2003; 52(8): 2007 - 2015. [Abstract] [Full Text] [PDF]