Heterogeneity among resident murine peritoneal macrophages: separation and functional characterization of monocytoid cells producing granulocyte-macrophage colony-stimulating factor (GM-CSF) and responding to regulation by lactoferrin.

Abstract

Abstract Analysis of GM-CSF production by unstimulated, resident murine peritoneal cells after velocity sedimentation separation indicated the presence of 2 GM-CSF-producing monocytoid cell populations. The 1st population of ceils sedimented over a range of 5.8 to 8.0 mm/hr and consisted primarily of large and medium-size adherent, phagocytic, nonspecific esterase-positive, Fc receptor-bearing monocytes and macrophages. The 2nd GM-CSF-producing cell population had a mean sedimentation velocity of 4.0 mm/hr and consisted of Fc receptor-positive, weakly phagocytic, esterase-positive, Thy-1.2-negative, GM-CSF-producing cells, which contained little detectable acid hydrolase or lysozyme activity. Morphologically, these cells appeared to consist primarily of small monocytes and less differentiated monocytoid-like cells. In the presence of iron-saturated lactoferrin, constitutive GM-CSF production was inhibited in those monocytoid cells sedimenting at 5.8 to 8.0 mm/hr but not in those sedimenting at 4.0 mm/hr. The ability of lactoferrin to inhibit GM-CSF production correlated directly with the ability of those cells to bind lactoferrin. The addition of bacterial lipopolysaccharide reversed the inhibitory effect of lactoferrin on the 5.8 to 8.0 mm/hr monocyte-macrophage population and returned GM-CSF production to control levels. No effect of LPS was observed on the 4.0 mm/hr cell population; however, enhancement of GM-CSF production from cells sedimenting at 1.0 to 3.0 mm/hr was noted. Lactoferrin was without effect on the production of a monocyte-macrophage-derived stimulating factor necessary for the generation of CFU-GM in suspension culture by either cell population. These results indicate that the regulation of monocyte-macrophage-derived hematopoietic relevant growth factors is complex and depends upon specific regulatory signals as well as specific subpopulations of monocytoid cells.