Priming of neutrophil oxidative responses by platelet-activating factor.
Platelet-activating factor is a potent proinflammatory lipid mediator which directly stimulates neutrophil chemotaxis, degranulation, aggregation, and superoxide radical (O2-) production. PAF also modifies or 'primes' neutrophil responses to other agents. Although a relatively weak direct oxidative agonist, PAF markedly enhances O2- release evoked by phorbol myristate acetate (PMA) and the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), increasing the maximal rate of O2- production by a calcium-dependent mechanism. PAF also increases protein kinase activity in the membrane fraction of neutrophils. In search of a mechanism for oxidative priming by PAF, we investigated the role of PAF in modifying PMA-induced activation/translocation of protein kinase C (PKC) in human neutrophils. In the presence of PAF and PMA both PKC and calcium-, phospholipid-independent protein kinase activities in particulate fractions increase markedly over activities detected in the presence of PMA alone. The increase in particulate protein kinase activities requires the presence of cytochalasin B and is calcium-dependent. The PKC-enhancing effect of PAF may be involved in the mechanism whereby the phospholipid 'primes' neutrophils for augmented oxidative responses to some stimuli but the exact role of PKC in neutrophil oxidative metabolism remains to be defined.
Gay
J C
JC
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232.
D000328:Adult; D003571:Cytochalasin B / Q000008:administration & dosage; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000008:administration & dosage; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000008:administration & dosage*; D011493:Protein Kinase C / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage
D010972:Platelet Activating Factor; D013481:Superoxides; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate