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Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF
S R McColl1, C Kreis, J F DiPersio
1Unité de Recherche, Inflammation et Immunologie-Rhumatologie, Centre Hospitalier de l'Université Laval, Sainte-Foy, Québec, Canada.
Abstract:
Pre-incubation of human neutrophils with pertussis toxin significantly inhibited the neutrophil-directed biologic actions of granulocyte-macrophage colony-stimulating factor (GM-CSF) in three separate assays: the induction of c-fos mRNA, the enhancement of both platelet-activating factor-induced mobilization of intracellular calcium, and stimulation of leukotriene synthesis by the calcium ionophore A23187. Cholera toxin did not have an effect on the latter two assays. Pre-treatment of human neutrophils with pertussis toxin did not affect the binding of GM-CSF to its surface receptor. These results provide the first evidence that a pertussis toxin substrate plays an important mediatory role in the mechanism of action of GM-CSF.