Dual function of monocytes on the regulation of granulopoiesis

The intrinsic balance of monocyte-derived mediators in the regulation of granulopoiesis was studied. Both the granulocyte macrophage colony-stimulating factors (GM-CSFs) and the colony inhibitory factor (prostaglandin E2; PGE2), were found to be elaborated by cultured monocytes, and most of these mediators were secreted during the first 4 days after monocyte cultivation. The concentration of monocytes in culture had a direct effect on the amount of mediator production. A maximum amount of mediators was noted to range from 2 x 10(5)-2 x 10(6) monocytes per 35 mm Petri dish. It was also found that the monocytes responded to the exogenous stimulus (lipopolysaccharide, LPS) in a biphasic manner. The optimal concentration of LPS in stimulating production of the tested mediators was 3.2 micrograms/ml. At higher concentrations (greater than 3.2 micrograms/ml), both the release of GM-CSFs and PGE2 were suppressed. The addition of indomethacin to the culture system resulted in a confirmatory increase in GM-CSFs production at LPS concentration higher than 3.2 micrograms/ml. The response of monocytes to endogenous regulators (GM-CSFs and PGE2) was also determined. The addition of GM-CSFs to the cultures promoted PGE2 production by monocytes in dose-dependent with an optimal concentration of around 450 units/ml. Alternatively, treatment of monocytes with PGE2 (10(-9) to 10(-10) M) also enhanced, to a certain extent, the production of GM-CSFs. The coincidence of the peaks of GM-CSFs and PGE2 release demonstrated in vitro suggested the existence of an intrinsic balance mechanism in the regulation of granulopoiesis by monocytes.