Evidence for complement-induced endothelial injury in vivo: a comparative ultrastructural tracer study in a controlled model of hyperacute rat cardiac allograft rejection.
In order to delineate the potential role of platelet-derived factors and of the direct lytic action of complement in the pathogenesis of endothelial injury in hyperacute allograft rejection, a highly reproducible and rigidly controlled inbred rat cardiac model was studied, utilizing colloidal carbon as a vascular tracer for comparative ultrastructural analysis of the microcirculation. Unmodified allografts were characterized by widespread intramural carbon labeling of the microvasculature, which corresponded to sites of platelet sequestration and extensive endothelial cell disintegration. Under conditions of recipient platelet depletion without concomitant complement depression, carbon-labeled segments of the microcirculation showed widespread endothelial cell disintegration, the ultrastructural features of which were similar to those observed in the unmodified allograft group. The microvasculature of syngeneic heart grafts transplanted to platelet-depleted recipients as well as all platelet-depleted recipients' own hearts showed no similar ultrastructural changes. It is thus concluded that the loss of cellular integrity of the microcirculatory endothelium in hyperacute rat cardiac allograft rejection is not a platelet-dependent phenomenon. The current ultrastructural data combined with previous morphologic studies provide strong evidence that the severe form of endothelial injury observed in this model is mediated by the direct action of activated complement components.
D000818:Animals; D001792:Blood Platelets / Q000276:immunology; D003176:Complement C3 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology*; D004546:Elapid Venoms / Q000008:administration & dosage; D004727:Endothelium / Q000098:blood supply / Q000473:pathology / Q000648:ultrastructure*; D006084:Graft Rejection; D016027:Heart Transplantation; D008833:Microcirculation; D009206:Myocardium / Q000276:immunology / Q000648:ultrastructure; D010976:Platelet Count; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D013997:Time Factors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D003176:Complement C3; D004546:Elapid Venoms