title: LPS-induced activation of primed murine peritoneal macrophages is modulated by prostaglandins and cyclic nucleotides.
abstract: Murine peritoneal macrophages primed in vivo by trehalose dimycolate (TDM) express cytostatic activity against tumor cells after treatment in vitro with 10 ng/ml lipopolysaccharide (LPS) during a 4-hr period (activation step). There is a strict correlation (P < 0.0001) between acquisition of antitumoral activity and induction of NO synthase quantified by its end products citrulline and NO2-. LPS also stimulates the release of cyclooxygenase products which exert a retroinhibitory action on NO synthase and cytostatic activities, as judged by an increase of both parameters by indomethacin (1 microM) and a decrease by externally added PGE2 (1 microM). LPS increases cellular and extracellular cAMP levels through an indomethacin-sensitive pathway, pointing to cAMP as a second messenger in the retroinhibitory action of LPS-induced prostaglandins. In fact, the addition of 8-bromo-cAMP or of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine during the activation step decreases NO synthase activity; however, at the same time these drugs increase the apparent efficiency of NO as an antitumor agent.
authors.affiliation: URA CNRS 1116, Université Paris-Sud, Orsay, France.
authors.forename: K
authors.initials: K
authors.lastname: Raddassi
authors.forename: J F
authors.initials: JF
authors.lastname: Petit
authors.forename: G
authors.initials: G
authors.lastname: Lemaire
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000502:physiology*; D000818:Animals; D002455:Cell Division; D002956:Citrulline / Q000378:metabolism; D003311:Cord Factors / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000166:cytology
chemical_list: D003311:Cord Factors; D008070:Lipopolysaccharides; D009573:Nitrites; D011453:Prostaglandins; D002956:Citrulline; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007213:Indomethacin