Humoral Human Xenoreactivity Against Isolated Pig Pancreatic Islets |
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Authors: | Tatsuya Kin Yoshiyuki Nakajima Yukio Aomatsu Hiromichi Kanehiro Michiyoshi Hisanaga Saiho Ko Takao Ohyama Hiroshige Nakano |
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Institution: | (1) First Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan, JP |
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Abstract: | It is widely believed that the hyperacute rejection of vascularized xenografts in the pig-to-human combination is triggered
by the binding of human preformed natural antibodies (PNAbs) to the Galα.(1,3)Gal epitope in pig endothelium and the subsequent
activation of complement. However, it remains poorly defined whether xenogeneic pig pancreatic islets are damaged by antibody
and complement-mediated mechanisms. We examined the expression of Galα(1,3)Gal on isolated adult pig islets and the presence
of PNAbs in normal human sera directed against islets, using immunofluorescence staining and confocal laser scanning microscopy.
The pig islets were not stained with Galα(1,3)Gal-specific lectin GSIB4; however, the exocrine cells reacted strongly with
GSIB4, indicating that the Galα(1,3)Gal epitope was highly expressed on exocrine cells, but not on islets. Human sera showed
weak reactivity of IgM and IgG class PNAbs to the islets, but strong reactivity to the exocrine cells. Furthermore, we investigated
the cytotoxic effect of human serum on pig islets using an in vitro model of pig-to-human islet transplantation. The incubation
of pig islets with normal human sera for 45 min resulted in less than 10% specific lysis despite the binding of PNAbs, whereas
exposure of porcine aortic endothelial cells to the same human sera caused 56% complement-mediated lysis, determined using
a MTT cytotoxic assay. These results support the view that pig islets might not undergo early antibody and complement-mediated
rejection in humans.
Received: July 8, 1999 / Accepted: May 30, 2000 |
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Keywords: | Pig islet Xenotransplantation Hyperacute rejection Human preformed natural antibody |
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