Macrophages and dendritic cells in normal and regenerating murine skeletal muscle

Abstract

Mononuclear phagocytes and MHC class II+ dendritic cells (DC) were identified in frozen sections of skeletal muscle using a panel of pan-specific antimacrophage (MOMA-2, SER-4, Mac-1, F4/80), anti-major histocompatibility complex (MHC) class II (M5/114) and anti-DC (NLDC-145, N418, M342) monoclonal antibodies. Uninjured and regenerating skeletal muscle were investigated in SJL/J and BALB/c mice, strains with known differences in muscle regenerative capacity. Resident tissue macrophages and MHC class II+ DC were present within uninjured mouse muscle. A subpopulation of DC were positive for the pan-DC markers, N418 and M342, and negative for the lymphoid DC marker NLDC-145. Following crush injury, the macrophage population increased by day 2, became marked by day 3, and had decreased by day 6. In contrast, the number of MHC class II+ cells around the injury site increased steadily after injury and remained high at day 6. The numbers of macrophages and DC detected by immunohistochemical staining were consistently higher in SJL/J than BALB/c muscles. This study confirms that macrophages are a significant component of normal murine skeletal muscle and that these cells increase dramatically after injury. Furthermore the data also reveal for the first time that DC are present in normal skeletal muscle and that MHC class II+ cells, including DC, increase after injury. The presence of DC in muscle has important implications for the understanding of the immunobiology of muscle and immune-mediated processes such as the host versus graft responses following muscle transplants and autoimmune diseases affecting this tissue.