Expression of Cell Adhesion Molecules in Inflammatory Myopathies and Duchenne Dystrophy

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Abstract
Cell adhesion molecules participate in target-effector cell interactions in cell-mediated cytotoxicity and in leukodiapedesis in inflammatory diseases. Two ligand-receptor pairs may play a role in the adhesion of cytotoxic T cells to their targets: 1) intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1), and 2) LFA-3 and CD2. We therefore immunolocalized these molecules in myopathies where there is evidence for T cell-mediated myocytotoxicity, namely inclusion body myositis, polymyositis, and Duchenne dystrophy. Autoaggressive inflammatory cells close to invaded muscle fibers showed an increased expression of ICAM-1 and LFA-1. The nonnecrotic muscle fibers invaded by autoaggressive cells expressed ICAM-1 where their surfaces faced the invading cells. That immunoreactivity for ICAM-1 on the invading cells was distinct from that on the opposite muscle fiber surface was established by colocalization of ICAM-1 with the sarcolemmal marker dystrophin (or β-spectrin) and was also confirmed by confocal microscopy. Leukodiapedesis in inflamed tissues is mediated by ICAM-1, LFA-3, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin associated with endothelial cells. In dermatomyositis ICAM-1 was strongly expressed on endothelial cells of perimysial arterioles and venules and on some perifascicular capillaries. In all the other myopathies ICAM-1 and LFA-3 expressions were increased on endothelia of capillaries surrounded by inflammatory cells. VCAM-1 was detected in few arterioles in all diseases. E-selectin was not detected at any site in any disorder. We conclude that ICAM-1 is strongly induced on the surfaces of nonnecrotic muscle fibers where they are invaded by autoaggressive cells and that it serves as an important ligand for these cells. The selective upregulation of ICAM-1 on endothelial cells in dermatomyositis suggests that this ligand is differentially activated in this disease.

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