Sarcolemmal complement membrane attack complex deposits during acute rejection of myofibers in nonhuman primates

Abstract

We have previously studied in nonhuman primates several aspects of the acute rejection of myofibers, including the histological characteristics, the mechanisms of myofiber elimination by the T cells, and the development of anti-donor antibodies. Here, we report the participation of the complement membrane attack complex (MAC) in this context. We used muscle sections of macaques from experiments of allogeneic muscle precursor cell transplantation with confirmed rejection of the graft-derived myofibers. Sections were stained with hematoxylin and eosin, alizarin red and for immunodetection of MAC, CD8, CD4, C3, C4d, and immunoglobulins. The prominent finding was the presence of sarcolemmal MAC (sMAC) deposits in biopsies with ongoing acute rejection or with recent acute rejection. The numbers of sMAC-positive myofibers were variable, being higher when there was an intense lymphocyte infiltration. Few sMAC-positive myofibers were necrotic or had evidence of sarcolemma permeation. The immunodetection of C3, C4d, and immunoglobulins did not provide significant elements. In conclusion, sMAC deposits were related to myofiber rejection. The fact that the vast majority of sMAC-positive myofibers had no signs of necrosis or sarcolemmal permeation suggests that MAC would not be harmful to myofibers by itself.