title: Endogenous nitric oxide production by human monocytic cells regulates LPS-induced TNF production.
abstract: The ability to produce nitric oxide (NO) of human monocytes macrophages is object of debate. While studying the regulation of tumor necrosis factor (TNF) synthesis induced by endotoxin (LPS) in a human cell line of monocyte origin (THP-1) and in human peripheral blood mononuclear cells (PBMC) we found an indirect evidence of such production. We showed that L-N-monomethyl-arginine (L-NMMA), an inhibitor of NO synthase, and hemoglobin, a chelator of NO, are able to significantly reduce TNF synthesis, indicating that NO production is induced by LPS and contributes to the induction of TNF. Since NO is a known cytostatic agent, we also studied the cytostatic effect of LPS, and demonstrated that it is reverted by L-NMMA. Although we were unable to show any nitrites/nitrates accumulation in the culture media, taken together our data give an indirect evidence of a physiologically relevant LPS-induced NO production in human monocytes-macrophages.
authors.affiliation: Laboratory of Neuroimmunology, Mario Negri Institute, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zinetti
authors.forename: G
authors.initials: G
authors.lastname: Fantuzzi
authors.forename: R
authors.initials: R
authors.lastname: Delgado
authors.forename: E
authors.initials: E
authors.lastname: Di Santo
authors.forename: P
authors.initials: P
authors.lastname: Ghezzi
authors.forename: M
authors.initials: M
authors.lastname: Fratelli
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D019323:omega-N-Methylarginine
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine