IR-induced muscle damage and MC degranulation in C4−/− mice. A, The mean number (±SEM) of injured muscle fibers per 50 fc is shown for 8 IR-treated C57BL/6 mice, 12 IR-treated C4−/− mice, 3 sham-treated C57BL/6 mice, and 4 sham-treated C4−/− mice in two separate experiments (*, p < 0.01 relative to wild type). B, The mean number (±SEM) of intact MCs per 20 LPF was quantitated for each group described in A. C and D, Representative histological sections from these experiments. C, Gastrocnemius muscle sections were stained with Masson's trichrome. Large numbers of injured muscle fibers were detected in the muscle of IR-treated C57BL/6 mice with serpigenous strands of actin/myosin and rhabdomyolysis (arrows, middle panel). Minimal irreversible damage occurred in sham-treated C57BL/6 mice (left panel) and IR-treated C4−/− mice (right panel). D, High-power (×50 objective) magnification fields of the chloroacetate esterase-positive MCs in the muscle of the three groups as in C. Many exocytosed granules were found in the extracellular milieu adjacent to the activated MCs in IR-treated C57BL/6 mice (middle panel). These exocytosed granules were rarely seen in sham-treated C57BL/6 mice (left panel) or IR-treated C4−/− mice (right panel).