Embryonic origin of the mouse macrophage.

Progenitor cells capable of giving rise to functional macrophages in in vitro culture were first detectable in the fetal yolk sac of the mouse between day 7 and 8 of gestation. Macrophage progenitors were not detectable outside the yolk sac until day 11. Although the early yolk sac contained macrophage precursors, no cells with the morphologic or functional characteristics of mouse promonocytes or more mature macrophages were observed. Promonocytes and macrophages were first identified in the 10-day yolk sac and 11-day fetal liver. These cells were characterized by surface receptors for lgG immunoglobulin, peroxidase activity (promonocytes), glass adherence, and phagocytosis of a large yeast particle (macrophages). From these observations, we conclude that the early fetal yolk sac is the embryonic site of origin of the macrophage precursor and that this precursor is “proximal” to the promonocyte on the pathway of sequential macrophage maturation. T HE BLOOD ISLANDS of the yolk sac are the first sites of hematopoiesis in both birds and mammals.’3 Hematopoietic stem cells, originating in these blood islands, migrate from the yolk sac into the circulation and subsequently colonize and proliferate within the hematopoietic organs of the developing embryo.”4 The hemopoietic stem cell content of yolk sac is demonstrable in experiments in which chick or mouse embryo yolk sac cells are used to repopulate both the myeloid and lymphoid tissues of irradiated recipients.2’5 Furthermore, multipotential stem cells detected by the in vivo spleen colony assay and progenitor cells of granulocytes and macrophages detected by the in vitro agar colony-forming assay have been demonstrated within the mouse yolk sac and subsequently within developing fetal liver.2 Recently, a bone marrow precursor of the monocyte-macrophage cell line has been identified in adult mice.6 This promonocyte has been characterized by its morphology, glass adhesiveness, limited phagocytic ability, DNAsynthetic capacity, and kinetic analysis of its relationship to more mature cells of this line.6’7 We have also recently observed that very primitive cells of the monocyte-macrophage line also possess the surface IgG-receptor that is characteristic of the monocyte and mature macrophage.8’3 On the basis of this series of observations, we undertook a study with the dual objectives of identifying the embryonic site of origin of the macrophage precursor and of determining whether this precursor was similar to the adult promonocyte.