Macrophages in developing mammalian skeletal muscle: evidence for muscle fibre death as a normal developmental event.

Macrophages in the diaphragm of fetal, growing and adult rats were investigated using electron microscopy. In addition, frozen sections of the diaphragm, muscles of the anterior abdominal wall and muscles of the calf were stained for acid phosphatase activity and examined with the light microscope. Macrophages were frequently observed in the muscles at 20 days of gestation and until the animals were 2 weeks old. They were less frequently found in the 4-week-old rats and very rarely found in the 8-week-old and adult rats. They were found in intimate contact with, sometimes apparently surrounding, certain muscle fibres which were very electron dense and considered to be degenerating. In addition, myofibrils were found as phagosomes within the macrophage cytoplasm. There was evidence to support the theory that macrophages develop from mesenchymal cells in embryonic tissue. Cells considered to be early macrophages and containing small lysosomes were found in the muscles at 16 and 18 days of gestation. In all other respects these cells resembled mesenchymal cells. It is proposed that cell death may be a normal developmental event in skeletal muscle, in which macrophages play an important role in the removal of the dead fibres.