Accelerated rate of mononuclear phagocyte production in vitro by splenocytes from autoimmune motheaten mice

The rapidly fatal autoimmune disease accompanied by pneumonitis in the mutant mouse known as motheaten is caused by an autosomal recessive gene. The proliferative capacity and production rate of splenic mononuclear phagocytes at different maturational stages, defined by morphologic criteria, were examined by two in vitro tritiated thymidine administration protocols and radioautography. The replicative rate of splenic promonocytes from 3-week-old normal mice was found to approximate that of adult bone marrow cells. Monocytes, macrophages, and previously described macrophagelike cells from motheaten mice had an accelerated rate of maturation in vitro, compared with similar cells from normal mice. These differences in the production rates could be attributed to the shorter period of time that promonocytes from the mutant mice are in the S phase of the cell cycle. Evidence, also, verified that the macrophagelike cells were derived from promonocytes via the monocyte-macrophage compartment. The unusual in vitro growth characteristics of the splenic mononuclear phagocytes from motheaten mice could be a manifestation of an in vivo abnormality of this lineage that could contribute to the development of pulmonary disease in these animals.