Modulation of the Rat Alveolar Macrophage Respiratory Burst by Hydroperoxides Is Calcium Dependent

Sublethal concentrations of hydroperoxides (H2O2or tert-butylhydroperoxide) produce a dual effect upon the respiratory burst of rat alveolar macrophages in which low concentrations (<50 μM) enhance and higher concentrations (>50 μM) produce inhibition (J. K. Murphy,et al., Free Radical. Biol....

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Bibliographic Details
Published in:Archives of biochemistry and biophysics Vol. 326; no. 1; pp. 166 - 171
Main Authors: Hoyal, Carolyn R., Gozal, Evelyne, Zhou, Huanfang, Foldenauer, Kim, Forman, Henry Jay
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-02-1996
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Summary:Sublethal concentrations of hydroperoxides (H2O2or tert-butylhydroperoxide) produce a dual effect upon the respiratory burst of rat alveolar macrophages in which low concentrations (<50 μM) enhance and higher concentrations (>50 μM) produce inhibition (J. K. Murphy,et al., Free Radical. Biol. Med.18, 37–45, 1995). These effects correlate with transient versus sustained elevation of [Ca2+]icaused by exposure to hydroperoxides prior to stimulation of the respiratory burst. In the present study changes in [Ca2+]icaused by exposure to sublethal levels of hydroperoxide were buffered by incubating macrophages with the acetoxymethyl ester of BAPTA, an intracellular Ca2+chelator. The enhancement of the phorbol ester-stimulated respiratory burst by tBOOH was abolished by BAPTA, while the inhibition was attenuated. Thus, the modulation by tBOOH appears to be largely dependent upon the changes in [Ca2+]i. Receptor mediated stimulation of the respiratory burst (ADP stimulation) involves release of Ca2+from the inositol-1,4,5-trisphosphate (IP3)-sensitive pool in the endoplasmic reticulum. Comparisons were made of the effects of thapsigargin (TG), an endoplasmic reticulum Ca-ATPase inhibitor, with tBOOH on release of intracellular Ca2+and the respiratory burst. Treatment with TG did not affect changes in [Ca2+]icaused by tBOOH or vice versa. Although TG decreased the ADP-stimulated respiratory burst, it had no effect upon tBOOH modulation. Thus, the effect of tBOOH upon the respiratory burst is dependent upon the release of Ca2+and the release of Ca2+occurs from a non-IP3-dependent pool. This aberrant mimicry of normal signal transduction underlies oxidative modulation of the respiratory burst.
ISSN:0003-9861
1096-0384
DOI:10.1006/abbi.1996.0061