Phagocytosis of necrotic muscle in muscle isografts is influenced by the strain, age, and sex of host mice

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Abstract
In grafts of skeletal muscle the implanted muscle becomes necrotic, is phagocytosed and replaced by new muscle cells. This study investigates the hypothesis that removal (phagocytosis) of necrotic implanted muscle is impaired in grafts made into old Swiss mice. Isografts (154) of minced muscle were made between young (20 day) and old (140 day) mice of the strains Swiss, AKR, BALBc, C3H and C57BL. Grafts were examined histologically after 7 days. A relationship between impaired phagocytosis and increasing host age was confirmed for male Swiss mice but was not seen with female Swiss mice or the other four strains. The proposal that ageing of bone marrow was responsible for diminished phagocytosis in old Swiss mice was investigated by replacing the marrow of 33 lethally irradiated male Swiss mice with marrow cells from mice of different ages (20 and 140 day), before isografting minced muscle. The results clearly show that macrophage stem cell function is unimpaired with age. Testosterone levels might account for the impaired phagocytosis seen in many sexually mature male Swiss mice. Support for this proposal came from experiments in which 15 mice were castrated before implanting muscle isografts. This study shows that genetic factors rather than the age of mice influenced phagocytosis and muscle formation in grafts.