Human monocytes maintained in culture acquire functional responsiveness to platelet-activating factor that is independent of increases in protein tyrosine phosphorylation

George Grigoriadis, Alastair G Stewart

Research output: Contribution to journalArticleResearchpeer-review

Abstract

1. Acute (day 0) stimulation with platelet-activating factor (PAF) did not elicit superoxide anion (O2-) generation from adherent monocytes. However by day 2 of culture, PAF induced an increase in O2- generation that was inhibited by pretreatment 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 ([Ca2+](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 O2- generation. In contrast, pretreatment with the protein kinase C inhibitor staurosporine had no effect on PAF-induced tyrosine phosphorylation, but did inhibit PAF-induced O2- 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 [Ca2+](i) or tyrosine phosphorylation.
Original languageEnglish
Pages (from-to)563 - 569
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Volume24
Issue number8
DOIs
Publication statusPublished - 1997

Cite this

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title = "Human monocytes maintained in culture acquire functional responsiveness to platelet-activating factor that is independent of increases in protein tyrosine phosphorylation",
abstract = "1. Acute (day 0) stimulation with platelet-activating factor (PAF) did not elicit superoxide anion (O2-) generation from adherent monocytes. However by day 2 of culture, PAF induced an increase in O2- generation that was inhibited by pretreatment 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 ([Ca2+](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 O2- generation. In contrast, pretreatment with the protein kinase C inhibitor staurosporine had no effect on PAF-induced tyrosine phosphorylation, but did inhibit PAF-induced O2- 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 [Ca2+](i) or tyrosine phosphorylation.",
author = "George Grigoriadis and Stewart, {Alastair G}",
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T1 - Human monocytes maintained in culture acquire functional responsiveness to platelet-activating factor that is independent of increases in protein tyrosine phosphorylation

AU - Grigoriadis, George

AU - Stewart, Alastair G

PY - 1997

Y1 - 1997

N2 - 1. Acute (day 0) stimulation with platelet-activating factor (PAF) did not elicit superoxide anion (O2-) generation from adherent monocytes. However by day 2 of culture, PAF induced an increase in O2- generation that was inhibited by pretreatment 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 ([Ca2+](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 O2- generation. In contrast, pretreatment with the protein kinase C inhibitor staurosporine had no effect on PAF-induced tyrosine phosphorylation, but did inhibit PAF-induced O2- 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 [Ca2+](i) or tyrosine phosphorylation.

AB - 1. Acute (day 0) stimulation with platelet-activating factor (PAF) did not elicit superoxide anion (O2-) generation from adherent monocytes. However by day 2 of culture, PAF induced an increase in O2- generation that was inhibited by pretreatment 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 ([Ca2+](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 O2- generation. In contrast, pretreatment with the protein kinase C inhibitor staurosporine had no effect on PAF-induced tyrosine phosphorylation, but did inhibit PAF-induced O2- 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 [Ca2+](i) or tyrosine phosphorylation.

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