The effect of lipopolysaccharide on the production of GM-EA, GM-CSA, and PGE2 by human monocyte-derived lipid-containing macrophages.

ABSTRACT

Monocyte-derived lipid-containing macrophage (MDLM) was the major source of granulomonopoietic enhancing activity (GM-EA) but these well-differentiated cells were unable to synthesize constitutively the granulocyte-macrophage colony-stimulating activity (GM-CSA) that was contributed mostly by the younger monocytoid cells. The presence of various concentrations (0.5-10 micrograms/ml) of lipopolysaccharide (LPS) potentiated the production of GM-EA by MDLM. Enhancement of GM-EA production peaked at about 0.5 micrograms/ml of LPS, but at higher doses (10-40 micrograms/ml) LPS became suppressive. In parallel, LPS-induced production of prostaglandin E2 (PGE2) was observable only at higher doses (10-40 micrograms/ml), suggesting a correlation between PGE2 production and LPS-mediated suppression of GM-EA synthesis. At optimal concentration (0.5 micrograms/ml), LPS could effectively override the inhibitory effect of interferon-gamma on the production of GM-EA. In addition, GM-CSA production by MDLM can be partly restored by stimulation with high doses of LPS (10-40 micrograms/ml). These results suggest that MDLMs have functional potentials similar to the younger macrophages and may play an important role in the regulation of myelopoiesis through the release of GM-EA and related regulators.