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HUMAN MONOCYTES MAINTAINED IN CULTURE ACQUIRE FUNCTIONAL RESPONSIVENESS TO PLATELET‐ACTIVATING FACTOR THAT IS INDEPENDENT OF INCREASES IN PROTEIN TYROSINE PHOSPHORYLATION
Author(s) -
Grigoriadis George,
Stewart Alastair G.
Publication year - 1997
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1997.tb02091.x
Subject(s) - tyrosine phosphorylation , platelet activating factor , phosphorylation , tyrosine kinase inhibitor , staurosporine , tyrosine kinase , tyrosine , protein kinase c , chemistry , protein phosphorylation , receptor tyrosine kinase , receptor , microbiology and biotechnology , endocrinology , medicine , biology , protein kinase a , biochemistry , cancer
SUMMARY 1. Acute (day 0) stimulation with platelet‐activating factor (PAF) did not elicit superoxide anion (02 ‐ ) generation from adherent monocytes. However, by day 2 of culture, PAF induced an increase in O2 ‐ generation that was inhibited by pretreat‐ment with the PAF receptor antagonist WEB 2086. 2. The lack of effect of PAF on O2 ‐ generation was not due to the absence of receptors, as PAF stimulated an increase in tyrosine phosphorylation and intracellular calcium ([Ca 2+ ] i ) on both days 0 and 2 of culture. 3. Pretreatment with the protein tyrosine kinase inhibitor methyl 2 ,5‐dihydroxycinnamate inhibited PAF‐induced tyrosine phosphorylation; however, this inhibitor failed to inhibit PAF‐induced O 2 ‐ generation. In contrast, pretreatment with the protein kinase C inhibitor staurosporine had no effect on PAF‐induced tyrosine phosphorylation, but did inhibit PAF‐induced O 2 ‐ generation. 4. These results indicate that monocytes maintained in culture acquire a functional response to PAF through a mechanism that appears to be independent of PAF receptor expression, coupling to increases in [Ca 2+ ] i or tyrosine phosphorylation.