Resolution of skeletal muscle inflammation in mdx dystrophic mouse is accompanied by increased immunoglobulin and interferon‐γ production

Abstract

Summary. Mdx mouse, the animal model of Duchenne muscular dystrophy, develops an X-linked recessive inflammatory myopathy with an apparent sustained capacity for muscle regeneration. We analysed whether changes in the skeletal muscle during myonecrosis and regeneration would correlate with functional alterations in peripheral lymphoid tissues. Here we show that during the height of myonecrosis, mdx mice display marked atrophy of peripheral lymph nodes and extensive muscle inflammation. In contrast, enlargement of draining lymph nodes with accumulation of CD4 CD44 , CD4 CD25 , CD8 CD44 T lymphocytes and type-2 B cells was consistently observed during amelioration of the muscle lesion. In addition, regeneration of the muscular tissue was accompanied by concomitant increase of immunoglobulin-secreting cells in regional lymph nodes and bone marrow. Double immunolabelling analysis revealed intense B cell proliferation and formation of germinal centre in the follicles of dystrophic regional lymph nodes. Furthermore, lymph node cells produced large amounts of IFN-g but not IL-4, IL-6 or IL-10 after in vitro mitogen stimulation with Concanavalin A. As these alterations occurred mainly during the recovery period, we suggested that local activation of the immune system could be an influence which mitigates the myonecrosis of muscular tissue in the mdx dystrophic mouse.

Extraocular muscle satellite cells are high performance myo-engines retaining efficient regenerative capacity in dystrophin deficiency

“…6D). In mdx 4cv EOM preparations, there was only a trend (but not a statistical difference, p =0.06) of CD45 + cell increase that could likely be explained by the overall increase in inflammatory cell production shown for mdx mice (Lagrota-Candido et al, 2002). Conversely, there was a decline in SC frequency in LIMB and DIA ( p <0.03) isolated preparations from mdx 4cv mice, while EOM preparations were unaffected ( p =0.09) when examining sorted populations (Fig.…”

Fast skeletal myofibers of mdx mouse, model of Duchenne muscular dystrophy, express connexin hemichannels that lead to apoptosis

“…Since cell death by necrosis, but not apoptosis, retrieves inflammatory cells, and since muscles of mdx mice are known to present necrosis and macrophage infiltration [34,39], we tested whether the absence of Cx43/Cx45 expression affects this phenomenon. Toward this aim, we evaluated the presence of inflammatory cells infiltrating muscular tissue through the evaluation of ED2 reactivity, which is a marker of mature macrophages [40].…”

Gender dimorphism influences extracellular matrix expression and regeneration of muscular tissue in mdx dystrophic mice

“…Although hypertrophied fibers and fibrosis are considered a characteristic histological feature (Lagrota-Cândido et al 2002) of older (48 weeks) mdx skeletal muscles (Fig. 2B) it is possible that such a pattern may be influenced by gender dimorphism.…”

“…Soon after birth the mdx mouse presents cycles of skeletal muscle necrosis and regeneration that become very active over the next 5 weeks but progress at a lower rate throughout the life of the animal. Yet, persistent fibrosis and accumulation of connective tissue is a characteristic feature of older mdx mice (Lefaucher and Sebille 1996;McGeachie and Grounds 1999;Lagrota-Cândido et al 2002).…”