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The regulation of neutrophil phospholipase A(2) by granulocyte-macrophage colony-stimulating factor and its role in priming superoxide production

Roberts, PJ; Williams, SL; Linch, DC; (1996) The regulation of neutrophil phospholipase A(2) by granulocyte-macrophage colony-stimulating factor and its role in priming superoxide production. BRIT J HAEMATOL , 92 (4) 804 - 814.

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Abstract

Experiments were performed to investigate the relative role of phospholipase A(2) (PLA(2)) in the activation and cytokine-mediated priming of neutrophil superoxide production. PLA(2) activity was measured with a radiometric assay which discriminates between PLA(2) and the downstream enzyme, 5-lipoxygenase. In cells that had not been primed by prior incubation with granulocyte-macrophage collony stimulating factor (GM-CSF), PLA(2) and NADPH oxidase were differentially stimulated by the chemotactic peptide N-formyl-met-leu-phe (FMLP), calcium ionophore, or phorbol ester. In addition, inhibition of PLA(2) by mepacrine (0-100 mu mol/l) did not concomitantly inhibit FMLP-stimulated superoxide production. These findings suggest that the activity of PLA(2) and NADPH oxidase may be uncoupled in the unprimed cell. In cells preincubated with GM-CSF, time- and dose-dependent priming of FMLP-stimulated PLA(2) responses were observed and inhibition of PLA(2) by mepacrine was accompanied by the inhibition of FMLP-stimulated superoxide production down to the level of unprimed cells, The effect of mepacrine was not due to inhibition of FMLP receptor expression, These data suggest that a mepacrine-sensitive PLA(2) may have a role in the GMCSF mediated printing of superoxide production, Using ionophore-stimulate PLA(2) activity as a model, we showed that Bordatella pertussis toxin did not inhibit GM-CSF mediated priming, demonstrating that a pertussis-sensitive GTP-binding protein does not mediate signal transduction from the GM-CSF receptor to PLA(2). The tyrosine kinase inhibitor, genestein, selectively inhibited GM-CSF primed but not unprimed PLA(2) activity, demonstrating that GM-CSF-mediated priming requires tyrosine kinase activity.

Type: Article
Title: The regulation of neutrophil phospholipase A(2) by granulocyte-macrophage colony-stimulating factor and its role in priming superoxide production
Keywords: arachidonate, phospholipase A(2), superoxide, granulocyte-macrophage colony-stimulating factor, priming, ARACHIDONIC-ACID, NADPH OXIDASE, GM-CSF, PHOSPHATIDIC-ACID, RESPIRATORY BURST, PERTUSSIS TOXIN, ACTIVATION, INVOLVEMENT, PROTEIN, DEGRANULATION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/42248
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