Involvement of a Botulinum Toxin-Sensitive 22-kDa G Protein in Stimulated Exocytosis of Human Neutrophils
WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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Studies of human peripheral blood neutrophils PMNs demonstrated that botulinum neurotoxin D BT-D ADP-ribosylates a 22-kDa PMN G protein G22k and inhibits the exocytosis of both specific and azurophilic granules stimulated by FMLP. Furthermore, this inhibition of PMN exocylosis by BT-D was found to be correlated with the degree of irreversible ADP-ribosylation of G22k by BT-D and to require modification of at least 85 of PMN G22k before significant inhibition of secretion is observed. Although both pertussis toxin and BT-D inhibited exocytosis in FMLP-stimulated PMNs, the inhibitory elects of the two toxins were found to be additive. Pertussis toxin and BT-D also inhibited Ca2 GTPGTP-Gamma s-induced secretion in digitonin-permeabilized PMNs, but there were distinct differences between the inhibitory effects of the two toxins. In contrast to ST-D, the exotoxin botulinum C3 was found to ADP-ribosylate primarily a 24- to 25-kD PMN protein, and it was not found to inhibit Ca2- and GTP-induced section in permeabilized PMNs. Ultrastructural studies of BT-D- treated PMNs showed an accumulation of distinct membrane-bound organelles in the periphery of the cells after FMLP stimulation, suggestive of a toxin-induced block in organelle-plasma membrane fusion. Taken together, these findings indicate that BT. D-sensitive G22k has a functional role In stimulated exocytosis of PMNs. Journal of lmmunology, 1994, 152 0000.
- Anatomy and Physiology