Granulocyte-macrophage colony-stimulating factor (GM-CSF) primes human neutrophils for enhanced phosphatidylcholine breakdown by phospholipase D.
GM-CSF has previously been shown to increase human neutrophil phospholipase D (PLD) activity in response to fMLP. To further define the mechanism by which GM-CSF up-regulates PLD activity, we investigated the effect of GM-CSF pretreatment of neutrophils on phosphatidylcholine breakdown in response to a receptor-coupled stimulus N-formyl-methionyl-leucyl-phenylalanine (fMLP) and to a receptor-independent stimulus phorbol-myristate-acetate (PMA). Treatment of 1-0-[3H]alkyl-2-acetyl-sn-glycero-3-phosphocholine-prelabeled human neutrophils with 200 pM GM-CSF for 1 hour at 37 degrees C led to a more rapid and increased accumulation (2-3 fold) of [3H]-alkyl-phosphatidic acid (or [3H]-alkyl-phosphatidylethanol when cells are stimulated in presence of 0.5% ethanol) in response to both fMLP or PMA. The data indicate GM-CSF up-regulates phosphatidylcholine hydrolysis by a PLD by interfering with the excitation-response coupling sequence at a site distal to the fMLP receptor.
Bourgoin
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S
Unité de Recherche Inflammation et Immunologie-Rhumatologie, Centre de Recherche du Centre hospitaler, l'Université Laval, Sainte-Foy, Qc, Canada.
Borgeat
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Poubelle
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PE
D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D010713:Phosphatidylcholines; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate