Membrane potential modulates release of tumor necrosis factor in lipopolysaccharide-stimulated mouse macrophages.

摘要: Lipopolysaccharide (LPS)-mediated synthesis of macrophage gene products such as tumor necrosis factor (TNF) is controlled by different signaling pathways. We investigated intracellular free Ca2+ (Ca2+ic) and the membrane potential early cellular responses to LPS their role in release TNF. In peritoneal macrophages RAW 269 mouse cell line, its biologically active moiety lipid A stimulated TNF but exerted no significant effects on these using Fura-2/Indo-1 measure Ca2+ic bis-oxonol, well patch-clamp technique monitor potential. contrast, platelet-activating transiently induced both an increase depolarization release. Increased extracellular K+ concentrations or K(+)-channel blockers, quinine, tetraethylammonium, barium chloride, inhibited LPS-stimulated alpha, accumulation cell-associated alpha found enzyme-linked immunosorbent assay analysis, did not inhibit mRNA accumulation. Concentrations quinine (greater than 125 microM) enhanced (25-85 mM) required production significantly depolarized macrophages. These results indicate a lack ion transport activities suggest important regulatory posttranscriptional