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

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Published in Immunology. 1999, vol. 97, no. 1, p. 173-80
Abstract 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.
Keywords AnimalsCobra Venoms/pharmacologyComplement C3/metabolismComplement Inactivator Proteins/pharmacologyComplement System Proteins/immunologyCytotoxicity, ImmunologicGraft Survival/drug effects/immunologyImmunoglobulin M/metabolismIslets of Langerhans Transplantation/immunologyMaleMiceMice, Inbred C57BLRatsRats, Sprague-Dawley
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PMID: 10447729
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Article (Published version) (257 Kb) - public document Free access
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Research groups Chirurgie viscérale (104)
Hépatologie chirurgicale (327)
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OBERHOLZER, José et al. Decomplementation with cobra venom factor prolongs survival of xenografted islets in a rat to mouse model. In: Immunology, 1999, vol. 97, n° 1, p. 173-80. https://archive-ouverte.unige.ch/unige:41200

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Deposited on : 2014-10-27

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