DEVELOPMENT, DIFFERENTIATION, AND MATURATION OF MACROPHAGES IN THE FETAL MOUSE-LIVER

Primitive macrophages emerged in the sinusoidal lumen of the fetal mouse liver at 10 days of gestation before the initiation of hepatic hematopoiesis and matured into fetal macrophages. In the culture of cell suspensions from the fetal liver with LP3-conditioned medium, monocyte colonies were formed, but monocytopoiesis was poor in the early stage of hepatic hematopoiesis in vivo. In the culture of cell suspensions obtained from the fetal liver at 10 days of gestation on the monolayer of a mouse bone marrow stromal cell line, ST2, primitive/fetal macrophage colonies were formed before the development of monocyte/macrophage colonies and showed differentiation of primitive macrophages into fetal macrophages without passing through the stage of promoncytes and monocytes. At this time, the fetal cardiovascular system was connected with the vitelline vein just before the formation of the liver. With the progress of gestation, a monocytic cell series was observed to develop and form a monocyte/macrophage population. This was confirmed by in vitro studies with an LP3-conditioned medium and on a monolayer of ST2. Thus, it appears that there exist two different macrophage populations, a primitive/fetal macrophage population and a monocyte/macrophage population in hepatic hematopoiesis. It also appears that fetal macrophages are differentiated from primitive macrophages which are colonized into the fetal liver from the yolk sac or which develop in loco, presumably from hematopoietic stem cells.