Development, differentiation, and proliferation of macrophages in the rat yolk sac

Immunohistochemical and immunoelectron microscopic investigation using anti-rat macrophage monoclonal antibody (mAb) RM-1 demonstrated the first emergence of immature macrophages within blood islands of fetal rat yolk sacs at fetal day 9. At fetal day 10, they matured into fetal macrophages, showed intense immunoreactivity to RM-1, developed lysosomal granules, endocytic vesicles or vacuoles, and extended fine cytoplasmic processes. By the rosetting assay with IgG-coated sheep erythrocyte antibody (IgG-EA), both the immature and mature fetal macrophages showed rosette formation and phagocytosis of IgG-EA, but they were negative for peroxidase (PO) reaction. At fetal day 11, fetal macrophages were observed in the mesenchymal layer of the yolk sacs. In the yolk sacs, no promonocytes or monocytes were observed, although there was a very minor population (less than 1%) of immature myeloid cells containing a few small PO-positive cytoplasmic granules from fetal day 11 on. After combination of the vitelline vessels to the embryonic cardiovascular system, fetal macrophages appeared in embryonic rat tissues. By [3H]thymidine autoradiography, yolk sac macrophages were demonstrated to possess a marked proliferative potential. These results suggest that fetal macrophages in the yolk sac differentiate from haematopoietic stem cells without passing through the promonocyte or monocyte stage, proliferate actively, and colonize the embryonic rat tissues.