Factors inducing mast cell accumulation in skeletal muscle.
It has been suggested that mast cells contribute to the phenotype of dystrophinopathies, but the mechanisms of their recruitment into the skeletal muscle remain hypothetical. The aim of this study is to quantify the presence of mast cells in muscle during the cellular events of myofibre degeneration and regeneration. For this purpose, we compare the mast cell profile in dystrophin-deficient mdx mice in which muscles exhibit spontaneous cycles of degeneration-regeneration from 3 weeks of age, with that in Swiss mice in which muscles were injured either by ischaemia or by notexin injection. Notexin is an A2-type phospholipase that rapidly disrupts myofibre plasma membranes, while ischaemia results in a slower process of degeneration. Both lesions are followed by a successful regeneration. In intact muscles, mast cell counts (mean +/- SEM/mm2) range from 1.8 +/- 1 to 4.3 +/- 1.6. The injection of notexin is far more potent in recruiting mast cells into damaged muscle than is ischaemia (118.5 +/- 13.0 vs 12.3 +/- 1.8/mm2). Thus we conclude that the early disruption of the myofibre membrane could elicit mast cell accumulation in skeletal muscle. This may explain the elevated number of mast cells observed in mdx muscles, as dystrophin deficiency is though to induce myofibre membrane leakage. On the other hand, mast cells are more numerous in muscles of young and adult mdx mice that are allowed to regenerate, than in muscles of older animals in which there is little regeneration and fibrosis develops. In injured muscles, the peak of mast cell number is at the onset of regeneration (by day 3 after notexin injection, and by day 11 after ischaemia), rather than during the phase of myofibre necrosis. Therefore, we suggest that the mast cells, through the effects of released mediators, could contribute to muscle regeneration.
Lefaucheur
J P
JP
Laboratoire de Physiologie, Atelier de Régénération Neuromusculaire, Faculté de Médecine Saint-Antoine, Paris, France.
Gjata
B
B
Sebille
A
A
D000818:Animals; D002452:Cell Count; D004396:Coloring Agents; D004546:Elapid Venoms / Q000378:metabolism; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology*; D009336:Necrosis; D009498:Neurotoxins / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D013045:Species Specificity
D004396:Coloring Agents; D004546:Elapid Venoms; D009498:Neurotoxins; C005082:notexin