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Influence of Extracellular Calcium on the Metabolism of Arachidonic Acid in Alveolar Macrophages
Author(s) -
Taylor Stephen M.,
Laegreid William W.,
Englen Mark D.,
Dani Ginger M.,
Silflow Ron M.,
Liggitt H. Denny,
Leid R. Wes
Publication year - 1990
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.48.6.502
Subject(s) - biology , extracellular , arachidonic acid , metabolism , calcium , arachidonic acid metabolism , pulmonary alveolus , alveolar macrophage , macrophage , biochemistry , microbiology and biotechnology , intermediary metabolism , immunology , medicine , in vitro , enzyme
Bovine alveolar macrophage metabolism of arachidonic acid (AA) via cyclooxygenase (CO) and lipoxygenase (LO) pathways is stimulus specific. Under standard conditions with RPMI‐1640 media containing 0.4 mM Ca 2+ , the calcium ionophore A23187 stimulates the release of both CO and LO products, whereas opsonized zymosan and phorbol myristate acetate (PMA) selectively stimulate the CO pathway in these cells. We have examined the effect of varying the extracellular concentration of calcium (0–2.4 mM) on the profiles of AA metabolites secreted with differing stimuli. All stimuli caused the release of CO products, even in the absence of calcium in the media. The magnitude of release was correlated with increasing extracellular calcium concentrations, indicating some dependence of phospholipase activation on extracellular calcium. However, there were notable differences between stimuli regarding the magnitude of CO product formation and dependence on extracellular Ca 2+ . No 5‐LO products were demonstrable with either zymosan or PMA at any concentration of extracellular calcium tested, and inhibition of CO by indomethacin did not result in 5‐LO product formation for these stimuli. The production of 5‐LO products in bovine alveolar macrophages by A23187 required extracellular calcium, demonstrating an absolute dependence for activation of the 5‐LO pathway on an influx of extracellular calcium. Our results indicate that intracellular and extracellular Ca 2+ have differing roles in the metabolism of AA down CO and LO pathways in bovine alveolar macrophages depending on the stimulus used. This regulation suggests that the pools of calcium required for activation of phospholipase A 2 (PLA 2 ) are not necessarily available for the 5‐LO enzyme.