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 - PubMed (original) (raw)

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

Lisa Ozmen et al. Diabetes. 2002 Jun.

Abstract

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 micromol/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 micromol/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.

PubMed Disclaimer

Similar articles

• Tirofiban and activated protein C synergistically inhibit the Instant Blood Mediated Inflammatory Reaction (IBMIR) from allogeneic islet cells exposure to human blood.
  Akima S, Hawthorne WJ, Favaloro E, Patel A, Blyth K, Mudaliar Y, Chapman JR, O'Connell PJ. Akima S, et al. Am J Transplant. 2009 Jul;9(7):1533-40. doi: 10.1111/j.1600-6143.2009.02673.x. Epub 2009 May 20. Am J Transplant. 2009. PMID: 19459790
• Isolated human islets trigger an instant blood mediated inflammatory reaction: implications for intraportal islet transplantation as a treatment for patients with type 1 diabetes.
  Bennet W, Groth CG, Larsson R, Nilsson B, Korsgren O. Bennet W, et al. Ups J Med Sci. 2000;105(2):125-33. doi: 10.1517/03009734000000059. Ups J Med Sci. 2000. PMID: 11095109 Review.
• Evidence for instant blood-mediated inflammatory reaction in clinical autologous islet transplantation.
  Naziruddin B, Iwahashi S, Kanak MA, Takita M, Itoh T, Levy MF. Naziruddin B, et al. Am J Transplant. 2014 Feb;14(2):428-37. doi: 10.1111/ajt.12558. Epub 2014 Jan 21. Am J Transplant. 2014. PMID: 24447621
• The role of the innate immunity in islet transplantation.
  Moberg L. Moberg L. Ups J Med Sci. 2005;110(1):17-55. doi: 10.3109/2000-1967-181. Ups J Med Sci. 2005. PMID: 15801685 Review.
• Low-molecular weight dextran sulfate abrogates the instant blood-mediated inflammatory reaction induced by adult porcine islets both in vitro and in vivo.
  Goto M, Johansson H, Maeda A, Elgue G, Korsgren O, Nilsson B. Goto M, et al. Transplant Proc. 2004 May;36(4):1186-7. doi: 10.1016/j.transproceed.2004.04.028. Transplant Proc. 2004. PMID: 15194411

Cited by

• Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation.
  Yue L, Li J, Yao M, Song S, Zhang X, Wang Y. Yue L, et al. Front Immunol. 2024 Sep 13;15:1455691. doi: 10.3389/fimmu.2024.1455691. eCollection 2024. Front Immunol. 2024. PMID: 39346923 Free PMC article. Review.
• Kupffer cells abrogate homing and repopulation of allogeneic hepatic progenitors in injured liver site.
  Abbas N, You K, Getachew A, Wu F, Hussain M, Huang X, Chen Y, Pan T, Li Y. Abbas N, et al. Stem Cell Res Ther. 2024 Feb 20;15(1):48. doi: 10.1186/s13287-024-03656-w. Stem Cell Res Ther. 2024. PMID: 38378583 Free PMC article.
• Protocol for transplanting pancreatic islets into the parametrial fat pad of female mice.
  Tedla MG, Wright N, Yolcu ES, Wang Y, Shirwan H. Tedla MG, et al. STAR Protoc. 2024 Mar 15;5(1):102816. doi: 10.1016/j.xpro.2023.102816. Epub 2024 Jan 4. STAR Protoc. 2024. PMID: 38180833 Free PMC article.
• Engineering pancreatic islets with a novel form of thrombomodulin protein to overcome early graft loss triggered by instant blood-mediated inflammatory reaction.
  Turan A, Zhang L, Tarique M, Ulker V, Arguc FN, Badal D, Yolcu ES, Shirwan H. Turan A, et al. Am J Transplant. 2023 May;23(5):619-628. doi: 10.1016/j.ajt.2023.02.021. Epub 2023 Mar 1. Am J Transplant. 2023. PMID: 36863480 Free PMC article.
• The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells?
  Naqvi RA, Naqvi AR, Singh A, Priyadarshini M, Balamurugan AN, Layden BT. Naqvi RA, et al. Front Endocrinol (Lausanne). 2023 Jan 5;13:1001041. doi: 10.3389/fendo.2022.1001041. eCollection 2022. Front Endocrinol (Lausanne). 2023. PMID: 36686451 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.
  • Silverchair Information Systems

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program