Bacterial lipopolysaccharide up-regulates platelet-activating factor-stimulated Ca2+ mobilization and eicosanoid release in human Mono Mac 6 cells.
When human monocytic Mono Mac 6 cells were treated with bacterial LPS (10 ng/ml, 72 h), they showed an increase in phagocytic activity, superoxide anion production, and expression of monocyte/macrophage-associated cell surface Ag. In these more mature (LPS-treated) cells but not in untreated cells, platelet-activating factor (PAF) (100 nM) produced a three- to fourfold increase in cytosolic free Ca2+ concentration. The cytosolic free Ca2+ concentration increase was inhibited by the PAF receptor antagonist L-659,989 (10 microM) and by EGTA (2 mM), indicating receptor-dependent Ca2+ influx. Furthermore, L-659,989 (10 microM), as well as PAF (1 microM), inhibited specific [3H]PAF binding in LPS-treated but not in untreated cells. Consistent with these results, PAF (100 nM) stimulated release of arachidonic acid and thromboxane B2 only in LPS-treated cells, and this could be inhibited by L-659,989 (10 microM) and EGTA (2 mM). Our data indicate that LPS up-regulates PAF-induced Ca2+ influx, resulting in arachidonic acid and eicosanoid release in Mono Mac 6 cells.
Aepfelbacher
M
M
Institut für Prophylaxe und Epidemiologie, Kreislaufkrankheiten, München, Germany.
Ziegler-Heitbrock
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Lux
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Weber
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D000954:Antigens, Surface / Q000032:analysis; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D015777:Eicosanoids / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010587:Phagocytosis; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D015854:Up-Regulation
D000954:Antigens, Surface; D015777:Eicosanoids; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D013481:Superoxides; D016718:Arachidonic Acid; D013929:Thromboxane B2; D002118:Calcium