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 products that promote thrombosis, inflammation, and the healing of wounds. Whether 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 platelets modulated the endothelial cells. Whereas resting human platelets caused little change in normal porcine endothelial cells, platelets activated with small amounts of thrombin induced striking changes in the endothelial cells, 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 surface and were modified by the secretion of transforming growth factor-beta (TGF-beta).


CONCLUSIONS
These findings may explain how the activation of platelets at an early point in the rejection of vascularized organ xenografts or in chronic diseases might contribute to thrombotic, ischemic, and inflammatory changes characteristic of an organ xenograft undergoing rejection.
Bustos
M
M
Department of Surgery, Universidad de Bavarra, Pamplona, Spain.
Saadi
S
S
Platt
J L
JL
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D019040:E-Selectin / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006084:Graft Rejection / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015539:Platelet Activation; D013552:Swine; D013925:Thromboplastin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014183:Transplantation, Heterologous
D019040:E-Selectin; D019332:Endothelin-1; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D013925:Thromboplastin