Ontogenetic development, differentiation, and phenotypic expression of macrophages in fetal rat lungs.

Development, differentiation, and distribution of macrophages in fetal rat lungs were investigated immunohistochemically using anti-rat macrophage monoclonal antibodies. In the lung buds, RM-1+ macrophages were first detected on fetal day 13, and some showed reactivity for TRPM-2. They populated in the peribronchial mesenchyme of the lung buds, proliferated in loco, and showed no peroxidase activity in any intracellular organelles. Their immunophenotypic and ultrastructural features were consistent with those of primitive/fetal macrophages. By fetal day 16, some of them expressed ED1, but ED1+ cells were a minor subpopulation throughout the fetal period. On fetal day 18, ED2+ macrophages developed; some also were positive for RM-1, but the others were negative. Both the RM-1+ and ED2+ macrophages were major macrophage subpopulations and expressed Ki-M2R and/or TRPM-3; ED2+ and/or Ki-M2R+ cells are regarded as pulmonary interstitial resident macrophages. In organ culture, a similar expression of differentiation antigens by macrophages was confirmed. None of these macrophages cytochemically showed any peroxidase activity in vivo or in vitro. In the fetal stage, both RM-1+ and ED2+ macrophage subpopulations showed proliferative potential, suggesting their ability to proliferate and survive in vivo.