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Am J Physiol Lung Cell Mol Physiol 264: L523-L532, 1993;
1040-0605/93 $5.00
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AJP - Lung Cellular and Molecular Physiology, Vol 264, Issue 5 523-L532, Copyright © 1993 by American Physiological Society


ARTICLES

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

J. K. Murphy and H. J. Forman
Cell Biology Group of Childrens Hospital Los Angeles, California 90027.

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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