title: Mitogen-activated human mononuclear cells suppress calcium binding by sarcoplasmic reticulum.
abstract: Weakness in inflammatory myopathy is commonly more prominent than is muscle fiber necrosis, suggesting additional explanations for its origin. Recent studies reveal that cell-mediated immune mechanisms are active in PMS-DMS. In experiments reported here, the effect of human mononuclear cell-derived mediator-rich supernatant upon calcium accumulation by SR membranes was examined. SR, by triggered binding and release of calcium in the vicinity of myofibrils, plays a key role in regulation of skeletal muscle contraction and relaxation. SR was derived from Lewis and Sprague-Dawley rat pelvic girdle muscles. Mediator-rich supernatants were generated by exposure of Hypaque-Ficoll-purified human mononuclear cells to PHA-P and Con-A during 72 hr of incubation in RPMl 1640 medium containing 10% autologous serum. Mitogens alone were without effect on SR. Suppression of ATP-dependent calcium accumulation was demonstrable within 40 min of exposure of SR to mediator-rich supernatants. The factor(s) producing suppression of calcium binding was nondialyzable, stable on storage at -70 degrees C, and active upon SR at physiologic calcium-loading levels. These findings may have important implications for understanding of the mechanism of weakness in inflammatory myopathies.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D037102:Lectins / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011917:Rats, Inbred Lew; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D037102:Lectins; D009124:Muscle Proteins; D003208:Concanavalin A; D002118:Calcium