Mitogen-activated human mononuclear cells suppress calcium binding by sarcoplasmic reticulum
Kalovidouris, A.E.; Johnson, R.L.
Journal of Laboratory and Clinical Medicine 95(1): 144-154
1980
ISSN/ISBN: 0022-2143 PMID: 6965302 Document Number: 158027
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.