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.
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Authors | K Raddassi, B Berthon, J F Petit, G Lemaire |
Journal | Cellular immunology
(Cell Immunol)
Vol. 153
Issue 2
Pg. 443-55
(Feb 1994)
ISSN: 0008-8749 [Print] Netherlands |
PMID | 7509725
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cord Factors
- Lipopolysaccharides
- Recombinant Proteins
- Terpenes
- Calcimycin
- Ionomycin
- Thapsigargin
- Interferon-gamma
- Nitric Oxide Synthase
- Amino Acid Oxidoreductases
- Calcium-Transporting ATPases
- Calcium
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Topics |
- Amino Acid Oxidoreductases
(biosynthesis)
- Animals
- Calcimycin
(pharmacology)
- Calcium
(metabolism)
- Calcium-Transporting ATPases
(antagonists & inhibitors)
- Cord Factors
(pharmacology)
- Cytotoxicity, Immunologic
(drug effects)
- Enzyme Induction
(drug effects)
- Humans
- In Vitro Techniques
- Interferon-gamma
(pharmacology)
- Ionomycin
(pharmacology)
- Lipopolysaccharides
(pharmacology)
- Macrophage Activation
(drug effects, physiology)
- Macrophages, Peritoneal
(drug effects, immunology, metabolism)
- Mice
- Nitric Oxide Synthase
- Recombinant Proteins
- Signal Transduction
- Terpenes
(pharmacology)
- Thapsigargin
- Tumor Cells, Cultured
(immunology)
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