Diabetes, Vol 48, Issue 10 1907-1914, Copyright © 1999 by American Diabetes Association

ARTICLES

Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation?

W Bennet, B Sundberg, CG Groth, MD Brendel, D Brandhorst, H Brandhorst, RG Bretzel, G Elgue, R Larsson, B Nilsson and O Korsgren
Department of Transplantation Surgery, Karolinska Institutet, Huddinge Hospital, Sweden. william.bennet@transpl.hs.sll.se

The remarkable difference in success rates between clinical pancreas transplantation and islet transplantation is poorly understood. Despite the same histocompatibility barrier and similar immunosuppressive treatments in both transplantation procedures, human intraportal islet transplantation has a much inferior success rate than does vascularized pancreas transplantation. Thus far, little attention has been directed to the possibility that islets transplanted into the blood stream may elicit an injurious incompatibility reaction. We have tested this hypothesis in vitro with human islets and in vivo with porcine islets. Human islets were exposed to nonanticoagulated human ABO-compatible blood in surface-heparinized polyvinyl chloride tubing loops. Heparin and/or the soluble complement receptor 1 (sCR1) TP10 were tested as additives. Adult porcine islets were transplanted intraportally into pigs, and the liver was recovered after 60 min for immunohistochemical staining. Human islets induced a rapid consumption and activation of platelets. Neutrophils and monocytes were also consumed, and the coagulation and complement systems were activated. Upon histological examination, islets were found to be embedded in clots and infiltrated with CD11+ leukocytes. Furthermore, the cellular morphology was disrupted. When heparin and sCR1 were added to the blood, these events were avoided. Porcine islets retrieved in liver biopsies after intraportal islet allotransplantation showed a morphology similar to that of human islets perifused in vitro. Thus, exposure of isolated islets of Langerhans to allogenic blood resulted in significant damage to the islets, a finding that could explain the unsatisfactory clinical results obtained with intraportal islet transplantation. Because administration of heparin in combination with a soluble complement receptor abrogated these events, such treatment would presumably improve the outcome of clinical islet transplantation by reducing both initial islet loss and subsequent specific immune responses.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				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]

				T. Eich, O. Eriksson, T. Lundgren, and the Nordic Network for Clinical Islet Transplantat Visualization of Early Engraftment in Clinical Islet Transplantation by Positron-Emission Tomography N. Engl. J. Med., June 28, 2007; 356(26): 2754 - 2755. [Full Text] [PDF]

				J. Lau, G. Mattsson, C. Carlsson, D. Nyqvist, M. Kohler, P.-O. Berggren, L. Jansson, and P.-O. Carlsson Implantation Site-Dependent Dysfunction of Transplanted Pancreatic Islets Diabetes, June 1, 2007; 56(6): 1544 - 1550. [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. H. Tai, P. Foster, A. Rosales, B. Feng, C. Hasilo, V. Martinez, S. Ramadan, J. Snir, C.W. J. Melling, S. Dhanvantari, et al. Imaging Islets Labeled With Magnetic Nanoparticles at 1.5 Tesla Diabetes, November 1, 2006; 55(11): 2931 - 2938. [Abstract] [Full Text] [PDF]

				N. V. Evgenov, Z. Medarova, J. Pratt, P. Pantazopoulos, S. Leyting, S. Bonner-Weir, and A. Moore In Vivo Imaging of Immune Rejection in Transplanted Pancreatic Islets Diabetes, September 1, 2006; 55(9): 2419 - 2428. [Abstract] [Full Text] [PDF]

				A. S. Narang and R. I. Mahato Biological and biomaterial approaches for improved islet transplantation. Pharmacol. Rev., June 1, 2006; 58(2): 194 - 243. [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]

				E. D'Amico, H. Hui, N. Khoury, U. Di Mario, and R. Perfetti Pancreatic {beta}-cells expressing GLP-1 are resistant to the toxic effects of immunosuppressive drugs J. Mol. Endocrinol., April 1, 2005; 34(2): 377 - 390. [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]

				G. Mattsson, L. Jansson, A. Nordin, A. Andersson, and P.-O. Carlsson Evidence of Functional Impairment of Syngeneically Transplanted Mouse Pancreatic Islets Retrieved from the Liver Diabetes, April 1, 2004; 53(4): 948 - 954. [Abstract] [Full Text] [PDF]

				L. Ozmen, K. N. Ekdahl, G. Elgue, R. Larsson, O. Korsgren, and B. Nilsson 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 Diabetes, June 1, 2002; 51(6): 1779 - 1784. [Abstract] [Full Text] [PDF]

				A. Fox-Marsh and L. C. Harrison Emerging evidence that molecules expressed by mammalian tissue grafts are recognized by the innate immune system J. Leukoc. Biol., March 1, 2002; 71(3): 401 - 409. [Abstract] [Full Text] [PDF]

				B. Ritz-Laser, J. Oberholzer, C. Toso, M.-C. Brulhart, K. Zakrzewska, F. Ris, P. Bucher, P. Morel, and J. Philippe Molecular Detection of Circulating {beta}-Cells After Islet Transplantation Diabetes, March 1, 2002; 51(3): 557 - 561. [Abstract] [Full Text] [PDF]

				A. Pileggi, R. D. Molano, T. Berney, P. Cattan, C. Vizzardelli, R. Oliver, C. Fraker, C. Ricordi, R. L. Pastori, F. H. Bach, et al. Heme Oxygenase-1 Induction in Islet Cells Results in Protection From Apoptosis and Improved In Vivo Function After Transplantation Diabetes, September 1, 2001; 50(9): 1983 - 1991. [Abstract] [Full Text] [PDF]

				A.M. J. Shapiro, J. R.T. Lakey, E. A. Ryan, G. S. Korbutt, E. Toth, G. L. Warnock, N. M. Kneteman, and R. V. Rajotte Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus Using a Glucocorticoid-Free Immunosuppressive Regimen N. Engl. J. Med., July 27, 2000; 343(4): 230 - 238. [Abstract] [Full Text] [PDF]