Endogenous nitric oxide production by human monocytic cells regulates LPS-induced TNF production.
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.
Zinetti
M
M
Laboratory of Neuroimmunology, Mario Negri Institute, Milano, Italy.
Fantuzzi
G
G
Delgado
R
R
Di Santo
E
E
Ghezzi
P
P
Fratelli
M
M
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
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine