Release of heparan sulfate from endothelial cells. Implications for pathogenesis of hyperacute rejection

doi:10.1084/jem.171.4.1363

3rd Skeletal Biology and Medicine Symposium

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Release of heparan sulfate from endothelial cells. Implications for pathogenesis of hyperacute rejection

JL Platt, GM Vercellotti, BJ Lindman, TR Oegema Jr, FH Bach and AP Dalmasso
Department of Pediatrics, University of Minnesota, Minneapolis 55455.

Heparan sulfate proteoglycan associated with endothelial cells in normal blood vessels inhibits intravascular coagulation and egress of blood cells and plasma proteins, key features of hyperacute rejection. It was shown herein that exposure of cultured porcine endothelium to human serum as a source of natural antibodies and complement caused cleavage and release of 5% of endothelial cell proteoglycans within 4 min and greater than 50% within 1 h. Proteoglycan release depended on activation of the classical complement pathway and preceded irreversible cell injury. These findings suggest that loss of endothelial cell proteoglycan may be a critical step in the pathogenesis of hyperacute rejection and in diseases involving humoral injury to endothelial cells.
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