EVIDENCE FOR COMPLEMENT-INDUCED ENDOTHELIAL INJURY INVIVO - A COMPARATIVE ULTRASTRUCTURAL TRACER STUDY IN A CONTROLLED MODEL OF HYPERACUTE RAT CARDIAC ALLOGRAFT-REJECTION

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 106  (3) , 378-387
Abstract
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 effective recipient C3 [complement component 3] depletion by anticomplementary cobra venom factor, the allograft microcirculation showed no ultrastructural alterations when compared with unmodified syngeneic heart graft controls. Under conditions of recipient platelet depletion without concomitant complement depression, C-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 and all platelet-depleted recipients'' own hearts showed no similar ultrastructural changes. The loss of cellular integrity of the microcirculatory endothelium in hyperacute rat cardiac allograft rejection is apparently not a platelet-dependent phenomenon. The severe form of endothelial injury observed in this model is probably mediated by the direct action of activated complement components.