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Bradykinin stimulates phosphoinositide turnover and phospholipase C but not phospholipase D and NADPH oxidase in human neutrophils
Author(s) -
Catz Sergio D.,
SterínSpeziale Norma B.
Publication year - 1996
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.59.4.591
Subject(s) - nadph oxidase , phospholipase c , protein kinase c , signal transduction , bradykinin , chemotaxis , superoxide , phospholipase , phosphorylation , microbiology and biotechnology , phosphoinositide phospholipase c , biochemistry , phospholipase a2 , biology , staurosporine , oxidative phosphorylation , enzyme activator , gq alpha subunit , enzyme , g protein , receptor
In response to formyl‐Met‐Leu‐Phe (fMLP), human neutrophils (PMN) generate superoxide anion (O 2 ‐ ) by the enzyme complex NADPH oxidase. The modulation of phosphoinositide (PPI) turnover and the activation of phospholipases C (PLC) and D (PLD) have been shown to be early steps in the oxidative response of fMLP‐stimulated PMN. Although the physiological nonapeptide bradykinin (BK) is involved in inflammation, its participation in PMN activation has not been properly studied. In this work, activation of signal transduction pathways that mediate the oxidative response, and the modulation of the NADPH oxidase activity by BK, are analyzed. A direct comparison between the signal transduction pathway induced by BK and fMLP is also made. BK was not able to elicit O 2 ‐ production by PMN. Nevertheless, several signal transduction pathways associated with PMN activation were triggered by BK. The nonapeptide induced the phosphorylation of prelabeled membrane PPI. This phenomenon was imitated by PMA and inhibited by H7 and staurosporine, thus suggesting the participation of protein kinase c (PKC). A loss of labeled [ 32 P]PPI was triggered by fMLP. The fact that both PMA and fMLP stimulated O 2 ‐ production but modulated PPI turnover in different ways, indicates that PPI labeling does not correlate with the oxidative response. Because PKC activation seemed to be a prerequisite for BK‐induced modulation of PPI turnover, PLC activation could act as an intermediate step in this mechanism. Our results show that BK activated a PIP 2 ‐PLC measured as the release of [ 3 H]IP 3 . On the contrary, a PC‐PLD was highly stimulated by fMLP but not by BK. The fact that BK induced PLC activity but neither that of PLD nor NADPH oxidase, whereas fMLP triggered the activation of both phospholipases and evoked the PMN respiratory burst, suggests that diacylglycerol (DAG) from PIP 2 as well as PA or PA‐derived DAG, synergize to trigger the PMN oxidative response. Finally, BK inhibited O 2 ‐ production by fMLP‐activated PMN in a time‐dependent manner. Since BK did not induce NO production by PMN, the inhibitory effect on the oxidative function was not due to ONOO ‐ formation. These data show that BK plays an important role in inflammation by modulating the PMN function.