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Dexamethasone lowers cytosolic pH in macrophages by altering alkalinizing pH‐regulatory mechanisms
Author(s) -
Nauclér Claes,
Sundler Roger,
Tapper Hans
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.67.6.876
Subject(s) - dexamethasone , glucocorticoid receptor , cytosol , glucocorticoid , endocrinology , chemistry , atpase , medicine , biology , microbiology and biotechnology , pharmacology , biochemistry , enzyme
The effect of dexamethasone on cytosolic pH (pH c ) in resident mouse peritoneal macrophages was investigated using the fluorescent probe 2′,7′‐ bis (carboxyethyl)‐5(6)‐carboxyfluorescein tetra‐acetoxymethyl ester (BCECF‐AM). Dexamethasone was found to significantly lower pH c and this reduction of pH c evolved gradually with time, was near maximal at 10 nM dexamethasone, and could be prevented by the glucocorticoid receptor antagonist RU‐38486. The lower pH c of dexamethasone‐treated cells was neither due to a reduction of cellular buffer capacity nor to an altered regulation of pH c by Na + /H + ‐exchange or by acidifying Na + ‐independent Cl − /HCO exchange, as assessed by studies of pH recovery after acute acid and alkali loads, respectively. Instead, an impaired pH c recovery by both the H + ‐ATPase and the alkalinizing Na + ‐dependent Cl − /HCO exchange was observed. This impairment was most likely not caused by an altered expression or localization of the 39‐κDa subunit of the proton pump. Dexamethasone treatment caused a reduction of pH c also in a HCO‐containing solution, suggesting that acid extrusion by both the H + ‐ATPase and Na + ‐dependent Cl − /HCO exchange is important for maintenance and regulation of macrophage resting pH c . The lowering of macrophage pH c might be one mechanism whereby glucocorticoids exert their anti‐inflammatory effects. J. Leukoc. Biol. 67: 876–884; 2000.