Modulation of the alveolar macrophage respiratory burst by hydroperoxides.
Exposure of alveolar macrophages to hydroperoxides (ROOH) inhibits subsequent stimulation of O2.- production (the respiratory burst). Previous studies (under nonoxidant stress conditions) have shown that elevation of intracellular free calcium ([Ca2+]i) participates in both initiation and termination of O2.- production. In this investigation, the effects of sublethal ROOH exposure on [Ca2+]i and the respiratory burst of rat alveolar macrophages were compared. Exposure to a sublethal range of H2O2 or tert-butylhydroperoxide (10-100 pmol/10(6) cells; initially 10-100 microM under the experimental conditions) for 15 min resulted in dose-dependent effects on the respiratory burst stimulated by various agents, ADP, ATP, zymosan-activated serum, and phorbol myristate acetate. Low concentrations of the ROOH (10 or 25 pmol/10(6) cells) were found to enhance stimulation, whereas exposure to 75 or 100 pmol/10(6) cells resulted in significant inhibition for all of the stimuli. All concentrations of ROOH caused a rapid elevation in [Ca2+]i. For those concentrations of ROOH that produced enhancement of subsequent stimulation of the respiratory burst, [Ca2+]i returned to near baseline before the end of the 15-min preincubation. The temporal- and concentration-dependent effects of ROOH on [Ca2+]i correlate with subsequent enhancement or inhibition of stimulated O2.- production. Similarities between the ROOH-induced changes in [Ca2+]i and the effect of [Ca2+]i changes in physiological regulation of the respiratory burst suggest a potential relationship.
Murphy
J K
JK
Department of Molecular Pharmacology & Toxicology, University of Southern California, Los Angeles 90033.
Hoyal
C R
CR
Livingston
F R
FR
Forman
H J
HJ
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D005609:Free Radicals; D010545:Peroxides; D013481:Superoxides; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium