Chemoattractant receptor-specific differences in G protein activation rates regulate effector enzyme and functional responses

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Abstract
The hypothesis that disparate neutrophil functional responses to various chemoattractants are regulated by receptor-specific rates of G protein activation was examined in HL-60 granulocytes. The initial rates of G protein activation and the affinity of receptor-stimulated G proteins for GTPγS in HL-60 membranes stimulated by fMet-Leu-Phe, C5a, and leukotriene B4 (LTB4) differed significantly among the chemoattractants, with a rank order of fMet-Leu-Phe > C5a > LTB4. Equilibrium GTPγS binding showed that all three chemoattractants activated a common pool of G proteins. Stimulation of phospholipasc D activation, measured as phosphatidylethanol generation, and superoxide release in intact cells also occurred with a rank order of fMet-Leu-Phe > C5a > LTB+. On the other hand, the rank order of reccptor affinities for ligand and of the EC50 of chemoattractant stimulation of GTPγS binding was C5a > LTB4 > fMet-Leu-Phe. C5a and LTB4 receptor densities were similar but were less than formyl peptide receptor density. Graded pertussis toxin treatment proportionally reduced superoxide release and phospholipase D activation to all three chemoattractants. The results suggest that receptor-specific differences in G pro tein affinity for guanine nucleotides lead to different rates of guanine nucleotide exchange and, thereby, contribute to disparate effector enzyme and functional responses. J. Leukoc. Biol 57: 679–686; 1995.

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