Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF.
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.
McColl
S R
SR
Unité de Recherche, Inflammation et Immunologie-Rhumatologie, Centre Hospitalier de l'Université Laval, Sainte-Foy, Québec, Canada.
Kreis
C
C
DiPersio
J F
JF
Borgeat
P
P
Naccache
P H
PH
D000001:Calcimycin; D002118:Calcium / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects; D016184:Receptors, Colony-Stimulating Factor; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D015289:Leukotrienes; D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D010566:Virulence Factors, Bordetella; D000001:Calcimycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium