Expression of extracellular matrix ligands and receptors in the muscular tissue and draining lymph nodes of mdx dystrophic mice.

Abstract

The mdx mouse, an animal model of Duchenne muscular dystrophy, develops an X-linked recessive inflammatory myopathy. During onset of disease and height of myonecrosis, mdx mice also display important changes in the microenvironment of lymphoid tissues. Draining lymph nodes showed reduced cellularity and atrophy accompanied by intense immunolabeling for fibronectin, laminin, and type-IV collagen. Following clinical amelioration of dystrophy, mdx mice showed enhanced cellularity and a consistent increase in the absolute numbers of CD4(+) and CD8(+) cells expressing alpha4(high) and alpha5(high) extracellular matrix receptors. Furthermore, infiltrating cells in the proximity of myonecrosis expressed alpha4, alpha5, and alpha6 integrin chains during both height of myonecrosis and muscular tissue regeneration. Such results indicate that during distinct phases of muscular dystrophy, altered expression of extracellular matrix ligands and receptors may be influencing myonecrosis by promoting adhesion and migration of mononuclear cells into the altered skeletal muscle and toward local draining lymphoid tissue.