Published online before print June 16, 2003

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© 2003 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1102537

Received for publication November 10, 2002.
Revised April 13, 2003.
Accepted for publication April 25, 2003.

Article

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

Institute of Biophysics, Chinese Academy of Sciences, Beijing

Abstract

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)P₃ production, PI-3K activation, and cytoplasmic Ca²⁺ mobilization were investigated. It was found that Ins(1,4,5)P₃ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ entry in the cells when Ca²⁺ release from the intracellular store was blocked by a PLC inhibitor, or a capacitative Ca²⁺ entry was induced by preincubation with thapsigargin. However, the AA-mediated, noncapacitative Ca²⁺ 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 and PLC, respectively, and the PI-3K signaling pathway are involved in the AA-stimulated respiratory burst in human neutrophil.

Key Words: signal transduction • calcium mobilization • calcium entry • U73122 • wortmannin

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