Premium
Phospholipase C and phosphatidylinositol 3‐kinase signaling are involved in the exogenous arachidonic acid‐stimulated respiratory burst in human neutrophils
Author(s) -
Liu Jiang,
Liu Zhaoxia,
Chuai Shaokun,
Shen Xun
Publication year - 2003
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 - 10.1189/jlb.1102537
Subject(s) - phosphatidylinositol , arachidonic acid , biology , respiratory burst , phospholipase c , microbiology and biotechnology , kinase , phospholipase d , signal transduction , phospholipase , protein kinase c , neutrophile , lipid signaling , phospholipase a2 , biochemistry , immunology , enzyme , in vitro
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 th 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 β and PLC γ , respectively, and the PI‐3K signaling pathway are involved in the AA‐stimulated respiratory burst in human neutrophil.