Natural Killer Cells and Macrophages in Immature Denervated Rat Muscles

Neonatally denervated muscle fibers of rat atrophy, degenerate, and eventually vanish unless they are reinnervated. Immunohistochemistry of hindlimb muscles denervated for 4 to 8 weeks showed OX8+ and also 3.2.3+ natural killer (NK) cells and ED1+ macrophages, which were much more frequent between atrophic non-reinnervated fibers than between reinnervated fibers. OX19+ T cells and OX33+ B cells were rare. Electron micrographs 4 to 15 weeks after denervation showed typical medium-sized lymphocytes and large lymphocytes with dense granules in close contact with muscle fibers of 1 to 3 μm diameter. Blunt projections of lymphocytes penetrated the basal lamina of the muscle fibers and established membrane contacts. The basal lamina of atrophic fibers had been invaded by slender projections of cytoplasm-rich stellate or fusiform cells, which seemed to strip them of their basal lamina. Thin fibers without basal lamina were engulfed by the stellate cells that in several aspects resembled fibrocytes but that presumably corresponded to the ED1+ macrophages seen by light microscopy. Electron microscopy and in situ nick translation demonstrated the rare appearance of apoplotic myonuclei. It is suggested that lymphocytes and macrophages are involved in the breakdown of neonatally denervated muscle fibers, and that apoptosis following contact with NK cells may represent the mode of cell death.