Modulation of leukotriene generation by pertussis toxin

The purpose of our study was to characterize the properties of the interaction of pertussis toxin with human polymorphonuclear leukocytes for the modulation of leukotriene generation and metabolism. The cells were stimulated with either the Ca ionophore A23187, opsonized zymosan, or the bacterial peptide formyl-methionyl-leucyl phenylalanine. Incubation of the cells with pertussis toxin led to a rapid inhibition of LTB4 generation when formyl-methionyl-leucyl phenylalanine was used as the stimulus, whereas there was no effect with the Ca ionophore and just a low effect with opsonized zymosan. The inhibition of leukotriene generation was dependent on the incubation time, temperature, and pertussis toxin concentration. The effect was not dependent on the presence of calcium. Incubation of the cells with guanosine 5'-O-(3-thiotriphosphate) the stable analog of GTP, led to a time-dependent increase in leukotriene generation induced by formyl-methionyl-leucyl phenylalanine which was abolished by the simultaneous addition of pertussis toxin. Our data suggest that the formyl-methionyl-leucyl phenylalanine-induced generation of leukotrienes is dependent on a GTP-binding protein. The participation of the various G proteins has yet to be elucidated.