Effects of sodium and proton pump activity on respiratory burst and pH regulation of rat alveolar macrophages

JK Murphy, HJ Forman - American Journal of Physiology …, 1993 - journals.physiology.org
JK Murphy, HJ Forman
American Journal of Physiology-Lung Cellular and Molecular …, 1993journals.physiology.org
At pH 7.4, extracellular Na+ removal inhibited the rat alveolar macrophage respiratory burst
(RB) stimulated by phorbol 12-myristate 13-acetate (PMA) or zymosan-activated serum
(ZAS). At pH 6.8, the RB was lower and decreased the Na+ effect. Amiloride inhibited the
ZAS RB independently of effects on Na (+)-H+ exchange, but did not affect PMA stimulation.
NBD-Cl, an H (+)-ATPase inhibitor, significantly inhibited the PMA or ZAS RB. Na+ removal
caused sustained elevation of intracellular free [Ca2+], which previous studies suggested …
At pH 7.4, extracellular Na+ removal inhibited the rat alveolar macrophage respiratory burst (RB) stimulated by phorbol 12-myristate 13-acetate (PMA) or zymosan-activated serum (ZAS). At pH 6.8, the RB was lower and decreased the Na+ effect. Amiloride inhibited the ZAS RB independently of effects on Na(+)-H+ exchange, but did not affect PMA stimulation. NBD-Cl, an H(+)-ATPase inhibitor, significantly inhibited the PMA or ZAS RB. Na+ removal caused sustained elevation of intracellular free [Ca2+], which previous studies suggested inhibits the RB. Intracellular pH (pHi) was lower at pHo 6.8 compared with pHo 7.4, but not altered by Na+ removal. PMA stimulation resulted in acidification corresponding with onset of superoxide production. At pHo 7.4, recovery to baseline pHi occurred that was not inhibited by amiloride or Na+ removal. In contrast, amiloride slowed pHi recovery after an exogenous acid load. Addition of H(+)-ATPase inhibitors, NBD-Cl or bafilomycin, following PMA stimulation or acid loading, inhibited pHi restoration. These studies suggest that pHi regulation following stimulation was mainly through a proton pump, whereas Na(+)-H+ exchange occurred only after greater acid loading. Nevertheless, Na+ and pH interacted to modulate the RB independent of Na(+)-H+ exchange.
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