Mononuclear cells from patients with polymyositis inhibit calcium binding by sarcoplasmic reticulum.

We have examined whether peripheral blood mononuclear cells from patients with polymyositis-dermatomyositis (PM-DM) incubated with autologous muscle release mediators that can affect the Ca2+ binding by sarcoplasmic reticulum (SR), the key regulator of muscle contraction. Peripheral blood mononuclear cells from 11 patients with early, active, and untreated PM-DM and from 20 controls were incubated with various dilutions (ranging from 1:60 to 1:4800 wt/vol) of autologous muscle homogenates. Mononuclear cells from eight of 11 patients with PM-DM underwent proliferation as assessed by 3H-thymidine incorporation into mononuclear cells (stimulation indices ranging from 3 to 14). Supernatants from muscle-stimulated mononuclear cells suppressed the adenosine triphosphate-dependent Ca2+ binding by SR membranes derived from rat skeletal muscles. Neither proliferative responses of mononuclear cells nor release of mediators suppressing calcium binding by SR was observed in mononuclear cell cultures of controls. The factor(s) producing suppression of calcium binding by SR was nondialyzable, and its effect on SR was concentration dependent. These results suggest that mononuclear cells in PM-DM are sensitized to autologous muscle and release a soluble factor(s) that inhibits the function of SR muscle membrane. These findings may have important implications in the pathogenesis of muscle weakness in PM-DM.