Platelet-mediated activation of endothelial cells: Implications for the pathogenesis of transplant rejection

Background. Platelets exert their normal functions at sites of endothelial disruption by plugging discontinuities in blood vessels and secreting produ cts that promote thrombosis, inflammation, and the healing of wounds. Wheth er platelets might induce these changes in xenograft blood vessels, leading to development of acute vascular rejection, has been uncertain. Methods. To examine the role of human platelets: in modulation of xenograft endothelium, pig endothelial cells were treated with human platelets. Results. Treatment of quiescent porcine endothelial cells with human platel ets modulated the endothelial cells. Whereas resting human platelets caused little change in normal porcine endothelial cells, platelets activated wit h small amounts of thrombin induced striking changes in the endothelial cel ls, including the induction of tissue factor activity, the expression of E- selectin, and the secretion of endothelin-1. These changes were induced, at least in part, by interleukin-1 (IL-1) associated with the platelet surfac e and were modified by the secretion of transforming growth factor-beta (TG F-beta). Conclusion. These findings may explain how the activation of platelets at a n early point in the rejection of vascularized organ xenografts or in chron ic diseases might contribute to thrombotic, ischemic, and inflammatory chan ges characteristic of an organ xenograft undergoing rejection.