J. Nath et al., INVOLVEMENT OF A BOTULINUM TOXIN-SENSITIVE 22-KDA G-PROTEIN IN STIMULATED EXOCYTOSIS OF HUMAN NEUTROPHILS, The Journal of immunology, 152(3), 1994, pp. 1370-1379
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 gr
anules stimulated by FMLP. Furthermore, this inhibition of PMN exocyto
sis by, BT-D was found to be correlated with the degree of irreversibl
e ADP-ribosylation of G22k by BT-D and to require modification of at l
east 85% of PMN G22k before significant inhibition of secretion is obs
erved. Although both pertussis toxin and BT-D inhibited exocytosis in
FMLP-stimulated PMNs, the inhibitory effects of the two toxins were fo
und to be additive. Pertussis toxin and BT-D also inhibited Ca2+/GTP/G
TPgammaS-induced secretion in digitonin-permeabilized PMNs, but there
were distinct differences between the inhibitory effects of the two to
xins. In contrast to BT-D, the exotoxin botulinum C3 was found to ADP-
ribosylate primarily a 24- to 25-kDa PMN protein, and it was not found
to inhibit Ca2+- and GTP-induced secretion in permeabilized PMNs. Ult
rastructural studies of BT-D-treated PMNs showed an accumulation of di
stinct membrane-bound organelles in the periphery of the cells after F
MLP stimulation, suggestive of a toxin-induced block in organelle-plas
ma membrane fusion. Taken together, these findings indicate that BT-D-
sensitive G22k has a functional role in stimulated exocytosis of PMNs.