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Granulocyte-macrophage colony-stimulating factor (GM-CSF) primes human neutrophils for enhanced phosphatidylcholine
S Bourgoin1, P Borgeat, P E Poubelle
1Unité de Recherche Inflammation et Immunologie-Rhumatologie, Centre de Recherche du Centre hospitaler, l'Université Laval, Sainte-Foy, Qc, Canada.
Abstract:
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.