A Crucial Role of L‐Selectin in C Protein–Induced Experimental Polymyositis in Mice

Objective To investigate the role of adhesion molecules in C protein–induced myositis (CIM), a murine model of polymyositis (PM). Methods CIM was induced in wild‐type mice, L‐selectin–deficient (L‐selectin−/−) mice, intercellular adhesion molecule 1 (ICAM‐1)–deficient (ICAM‐1−/−) mice, and mice deficient in both L‐selectin and ICAM‐1 (L‐selectin−/−ICAM‐1−/− mice). Myositis severity, inflammatory cell infiltration, and messenger RNA expression in the inflamed muscles were analyzed. The effect of dendritic polyglycerol sulfate, a synthetic inhibitor that suppresses the function of L‐selectin and endothelial P‐selectin, was also examined. Results L‐selectin−/− mice and L‐selectin−/−ICAM‐1−/− mice developed significantly less severe myositis compared to wild‐type mice, while ICAM‐1 deficiency did not inhibit the development of myositis. L‐selectin−/− mice that received wild‐type T cells developed myositis. Treatment with dendritic polyglycerol sulfate significantly diminished the severity of myositis in wild‐type mice compared to treatment with control. Conclusion These data indicate that L‐selectin plays a major role in the development of CIM, whereas ICAM‐1 plays a lesser role, if any, in the development of CIM. L‐selectin–targeted therapy may be a candidate for the treatment of PM.