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- W2279571949 abstract "Within the acidic inflammatory milieu, macrophages (mφs) must maintain their cytoplasmic pH (pHi) within a range conducive to optimal function. It was previously shown that metabolism of L-arginine at concentrations present in vitro in RPMI medium (1.14 mM) impairs the ability of mφ s to regulate pHi. However, concentrations of L-arginine in vivo reportedly range from ~ 100 µM in serum to ≤ 50 µM in wounds. To investigate the potential in vivo relevance of this inhibition, mφ pHi regulation was examined following incubation with low concentrations of L-arginine that mimic the inflammatory microenvironment, in the presence or absence of lipopolysaccharide (LPS). pHi regulation was evaluated as the ability of thioglycolate-elicited murine peritoneal mφ s to recover from an imposed cytoplasmic acid load. The mϕ pHi was measured using a pH- sensitive fluorescent probe. Following incubation for 2 h in the absence of LPS, the pHi recovery rate was equivalent in cells incubated with and without L-arginine. Coincubation with LPS, however, resulted in marked inhibition of pHi recovery at L-arginine concentrations as low as 12.5 µM. The inhibition was not due to LPS alone, since LPS without L-arginine was not inhibitory. Inhibition of pHi recovery was observed at LPS concentrations ranging from 10 ng/ml to 10 µg/ml. The L-arginine-de- pendent inhibition was apparent within 60 min of exposure to LPS, in both freshly harvested cells and cells preincubated for 2 h in the absence of L-arginine and then exposed to both L-arginine and LPS. Under conditions mimicking the in vivo setting, LPS-stimulated L- arginine metabolism impairs mφHi regulation. Modulation of pHi by this mechanism may compromise mφ function within the acidic microenvironment of inflammation." @default.
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- W2279571949 date "1992-10-01" @default.
- W2279571949 modified "2023-10-14" @default.
- W2279571949 title "Lipopolysaccharide impairs macrophage cytoplasmic pH regulation under conditions simulating the inflammatory microenvironment" @default.
- W2279571949 doi "https://doi.org/10.1002/jlb.52.4.395" @default.
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