Degradative activity of granzyme A on skeletal muscle proteins in vitro: a possible molecular mechanism for muscle fiber damage in polymyositis.

The importance of cytotoxic T lymphocytes (CTLs) in the autoimmune inflammatory myopathies, especially polymyositis (PM), has been emphasized. We have studied the degradative activity of granzyme A, a cytotoxic molecule with trypsin-like specificity in CTL granules, on several muscle proteins in vitro. Our study reveals that granzyme A hydrolyzes dystrophin, myosin, and nebulin, but not laminin, alpha-actinin, vinculin, and connectin in vitro. Among these proteins, nebulin is more susceptible to proteolysis, followed by dystrophin, myosin heavy chain, and myosin light chains, in that order. This result implies an important role of granzyme A in CTL-mediated muscle fiber damage in PM.