Relative roles of Na+/H+ exchange and vacuolar-type H+ ATPases in regulating cytoplasmic pH and function in murine peritoneal macrophages.

Two distinct mechanisms have been shown to mediate cytoplasmic pH (pHi) recovery in acid-loaded peritoneal macrophages (M phi s): Na+/H+ exchange and H+ extrusion by vacuolar-type (V-type) H+ ATPases. The present studies examined the relative roles of these two systems in maintaining pHi and cell function. Measurements of M phi pHi and superoxide (O2-) production in response to stimulation with 12-O-tetradecanoyl phorbol 13-acetate (TPA) were made at physiological or acidic extracellular pH (pHo) levels.

Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages.

The ability of macrophages (Møs) to function within an acidic environment has been shown to depend on cytoplasmic pH (pHi) regulation by vacuolar-type H+ ATPases. Møs metabolize L-arginine via an oxidative pathway that generates nitric oxide, nitrate, and nitrite. Since each of these products could potentially inhibit vacuolar-type H+ ATPases, we investigated the effect of L-arginine metabolism on Mø pHi regulation in thioglycolate-elicited murine peritoneal Møs.

Cytoplasmic pH regulation in monocytes and macrophages: mechanisms and functional implications.

Maintenance of cytoplasmic pH (pHi) within a narrow physiological range is critical to optimal cell function. Monocytes and macrophages (Møs) actively regulate their pHi through three distinct plasma membrane ion transport systems: (1) Na+/H+ exchange; (2) Na(+)-dependent anion exchange; and (3) vacuolar-type H+ ATPases. Alterations in the functional state of monocytes and Møs have been linked to changes in pHi and/or its regulation by these ion transport systems.

Modulation of the macrophage respiratory burst by an acidic environment: the critical role of cytoplasmic pH regulation by proton extrusion pumps.

Within the acidic milieu of an abscess or tumor, macrophages must be able to maintain their cytoplasmic pH (pHi) close to the physiologic range to ensure optimal cell function. Our recent studies have demonstrated that a proton-extrusion mechanism with the characteristics of an H+ adenosine triphosphatase mediates pHi recovery in acid-loaded macrophages. These studies were designed to examine the role of these H+ pumps in maintaining cell function in an acidic extracellular environment.