ENDOGENOUS NITRIC-OXIDE PRODUCTION BY HUMAN MONOCYTIC CELLS REGULATESLPS-INDUCED TNF PRODUCTION

The ability to produce nitric oxide (NO) of human monocytes macrophage s is object of debate, While studying the regulation of tumor necrosis factor (TNF) synthesis induced by endotoxin (LPS) in a human cell lin e of monocyte origin (THP-1) and in human peripheral blood mononuclear cells (PBMC) we found an indirect evidence of such production. We sho wed that L-N-monomethyl-arginine (L-NMMA), an inhibitor of NO synthase , and hemoglobin, a chelator of NO, are able to significantly reduce T NF synthesis, indicating that NO production is induced by LPS and cont ributes to the induction of TNF, Since NO is a known cytostatic agent, we also studied the cytostatic effect of LPS, and demonstrated that i t is reverted by L-NMMA. Although we were unable to show any nitrites/ nitrates accumulation in the culture media, taken together oar data gi ve an indirect evidence of a physiologically relevant LPS-induced NO p roduction in human monocytes-macrophages.