Involvement of a Botulinum Toxin-Sensitive 22-kDa G Protein in Stimulated Exocytosis of Human Neutrophils
Abstract
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/ GTP/GTP-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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1994
- Accession Number
- ADA277711
Entities
People
- Annette Powledge
- Daniel G. Wright
- Jayasree Nath
Organizations
- Walter Reed Army Institute of Research