Phospholipase C and phosphatidylinositol 3-kinase signaling are involved in the exogenous arachidonic acid-stimulated respiratory burst in human neutrophils

Liu, J.; Liu, Z.; Chuai, S.; Shen, X.

Journal of Leukocyte Biology 74(3): 428-437


ISSN/ISBN: 0741-5400
PMID: 12949247
DOI: 10.1189/jlb.1102537
Accession: 011143786

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To define the role of phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI-3K), signaling pathways in arachidonic acid (AA)-stimulated respiratory burst in human neutrophils, the AA-stimulated respiratory burst, Ins(1,4,5)P(3) production, PI-3K activation, and cytoplasmic Ca(2+) mobilization were investigated. It was found that Ins(1,4,5)P(3) production and PI-3K activity in AA-stimulated cells were increased in a dose-dependent manner. U73122, the PLC inhibitor, effectively inhibited the AA-stimulated respiratory burst and Ca(2+) release from the intracellular calcium store but not the activity of PI-3K, indicating the independence of PI-3K signaling on PLC activation. Wortmannin, the PI-3K inhibitor, at the concentration sufficient to inhibit PI-3K activity, can only partially inhibit Ca(2+) release from the internal store, indicating a partial regulation of PLC signaling by PI-3K and the existence of two pathways initiated by different PLC subfamilies. One is regulated by PI-3K activation, and the other is independent of PI-3K signaling. It was observed that AA could still induce a noncapacitative Ca(2+) entry in the cells when Ca(2+) release from the intracellular store was blocked by a PLC inhibitor, or a capacitative Ca(2+) entry was induced by preincubation with thapsigargin. However, the AA-mediated, noncapacitative Ca(2+) entry seems to play a little, if any, role in the stimulated respiratory burst. The present study suggests that the PLC signaling pathway, which may be activated by PLC(beta) and PLC(gamma), respectively, and the PI-3K signaling pathway are involved in the AA-stimulated respiratory burst in human neutrophil.