title: Role of calcium in the activation of mouse peritoneal macrophages: induction of NO synthase by calcium ionophores and thapsigargin.
abstract: Bacterial lipopolysaccharide (LPS) has been recognized as one of the most potent activating signals for mouse peritoneal macrophages. In macrophages primed by interferon-gamma (IFN-gamma) or trehalose dimycolate (TDM), LPS induces NO synthase and the events associated with a high nitric oxide output: antitumor and antiparasitic activities. In the present report, it is shown that drugs (calcium ionophores or thapsigargin) which elevate the concentration of cytosolic calcium, [Ca2+]i, induce NO synthase and antitumor activities in primed macrophages, mimicking LPS action. Calcium ionophores and thapsigargin trigger NO synthase activity in macrophages primed in vivo by TDM, in thioglycollate-elicited macrophages primed in vitro by IFN-gamma, and in IFN-gamma-treated EMT6 adenocarcinoma cells. However, activation of TDM-primed macrophages by LPS does not seem to involve calcium fluxes: (i) no change in [Ca2+]i was detectable in TDM-primed macrophages loaded with Fura-2 and exposed to LPS, and (ii) activation of TDM-primed macrophages by LPS can be obtained in the presence of 4 mM EGTA. NO synthase expression is thus controlled in primed macrophages by two different pathways; calcium ionophores can replace LPS but do not act through the same intracellular cascade.
authors.affiliation: URA CNRS 1116, Bâtiment 432, Université Paris Sud, Orsay, France.
authors.forename: K
authors.initials: K
authors.lastname: Raddassi
authors.forename: B
authors.initials: B
authors.lastname: Berthon
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 / Q000096:biosynthesis*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D003311:Cord Factors / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D019001:Nitric Oxide Synthase; D011994:Recombinant Proteins; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014407:Tumor Cells, Cultured / Q000276:immunology
chemical_list: D003311:Cord Factors; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D013729:Terpenes; D000001:Calcimycin; D015759:Ionomycin; D019284:Thapsigargin; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000252:Calcium-Transporting ATPases; D002118:Calcium