A CONTROLLED SERIAL ULTRASTRUCTURAL TRACER STUDY OF 1ST-SET CARDIAC ALLOGRAFT-REJECTION IN THE RAT - EVIDENCE THAT THE MICROVASCULAR ENDOTHELIUM IS THE PRIMARY TARGET OF GRAFT DESTRUCTION

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 111  (2) , 184-196
Abstract
To define the serial morphologic correlates of unmodified 1st-set cardiac allograft rejection in an inbred rat strain combination, a series of Wistar-Furth cardiac allografts transplanted to normal nonsensitized Lewis recipients were studied as a function of time with the use of well-documented ultrastructural tracer techniques. Colloidial carbon was employed as a vascular label for detection of microvascular endothelial structural alterations, and horseradish peroxidase was used as a tracer probe for localization of cell-membrane permeability dysfunction of allograft endothelium and cardiocytes and of elements of the cellular infiltrate. Wistar-Furth to Wistar-Furth syngeneic heart grafts and Wistar-Furth recipients'' own hearts provided appropriate control data. Severe diffusion loss of functional and structural integrity of the microvascular endothelium preceded the development of extensive damage to cardiac muscle cells and provided strong evidence that the allograft microcirculation is the primary target of immunologic injury. The sequential pattern of injurious changes present in the rejecting allografts was similar to that observed in certain models of delayed-type hypersensitivity and of skin graft rejection, raising the possibility that lymphokine-mediated mechanisms may be of major pathogenetic significance in this setting.