Decomplementation with cobra venom factor prolongs survival of xenografted islets in a rat to mouse model

Article Article scientifique Article Decomplementation with cobra venom factor prolongs survival of xenografted islets in a rat to mouse model eng 1999 author Oberholzer José 133896 author Yu Dong Mei 24252 author Triponez Frédéric 28673 author Cretin Nathalie 81849 author Andereggen Elisabeth Marie 32792 author Mentha Gilles 22892 author White Derek 29164 author Buehler Leo Hans 71923 author Morel Philippe 22337 author Lou Jinning 26933 173-180 10.1046/j.1365-2567.1999.00742.x 10447729 0019-2805 Although the involvement of complement in hyperacute rejection of xenotransplants is well recognized, its role in rejection of devascularized xenografts, such as pancreatic islets, is not completely understood. In this study, we investigated whether complement participates in the immunopathology of xeno-islet transplantation in a concordant rat to mouse model. Rat pancreatic islets were implanted under the kidney capsule of normal and cobra venom factor (CVF)-decomplementized diabetic C57BL/6 mice. Graft survival was monitored by blood glucose levels. Deposition of IgM and C3 on grafted islets in vivo or on isolated islets in vitro (after incubation with normal and decomplementized mouse serum), as well as CD4- and CD8-positive leucocyte infiltration of grafts, was checked by immunohistochemistry. In addition, complement-mediated cytotoxicity on rat islet cells was evaluated by a 3-(4, 5-dimethythiazolyl)-2.5-diphenyl-2H-tetrazolium-bromide (MTT) assay. A significant C3 deposition was found on grafted islets from the first day after transplantation in vivo, as well as on isolated islets after incubation with mouse serum in vitro. By MTT assay, complement-mediated cytotoxicity for islet cells was found. Decomplementation by CVF decreased C3 deposition on either isolated or grafted islets, delayed CD4- and CD8-positive leucocyte infiltration, led to significant inhibition of complement-mediated cytotoxicity for islet cells, and prolonged graft survival (mean survival time 21.3 versus 8.5 days; P<0.01). Our results indicate that decomplementation can prolong the survival time of devascularized xenografts across concordant species. The deposition of complement on transplanted islets may contribute to xenograft rejection by direct cytotoxicity and by promoting leucocyte infiltration. Animals Cobra Venoms/pharmacology Complement C3/metabolism Complement Inactivator Proteins/pharmacology Complement System Proteins/immunology Cytotoxicity, Immunologic Graft Survival/drug effects/immunology Immunoglobulin M/metabolism Islets of Langerhans Transplantation/immunology Male Mice Mice, Inbred C57BL Rats Rats, Sprague-Dawley Dewey 617 57 Département de chirurgie 222 false 79 Chirurgie viscérale 104 1329 Chirurgie viscérale (HUG) 249 Hépatologie chirurgicale 327 Immunology 97 1 f4e8687d-aea0-4bd2-ba4f-d2520c90f3c5 Article (Published version) Public j.1365-2567.1999.00742.x.pdf 263151 application/pdf openAccess Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Decomplementation with cobra venom factor prolongs survival of xenografted islets in a rat to mouse model	Immunology	1999	889	477
Smoothing of embeddings and classifying spaces		1971	131	0

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