Botulinum C2 toxin ADP-ribosylates actin and enhances 02 production and secretion but inhibits migration of activated human neutrophils

The binary botulinum C2 toxin ADP-ribosylated the actin of human neutrophils. Treatment of human neutrophils with bot-ulinum C2 toxin for 45 min increased FMLP-stimulated su-peroxide anion (O°) production 1.5-5-fold, whereas only a minor fraction of the cellular actin pool (- 20%) was ADP-ri-bosylated. Effects of botulinum C2 toxin depended on toxin concentrations, presence of both components of the toxin, and incubation time. Cytochalasin B similarly enhanced O2 pro-duction. The effects of botulinum C2 toxin and cytochalasin B were additive at submaximally, but not maximally effective concentrations and incubation time of either toxin. Botulinum C2 toxin also enhanced stimulation of O2 production by Con A and platelet-activating factor, but not by phorbol 12-myristate 13-acetate (PMA). Botulinum C2 toxin increased FMLP-in-duced release of N-acetyl-glucosaminidase by 100-250%; re-lease of vitamin B12-binding protein induced by FMLP and PMA was enhanced by- 150 and 50%, respectively. Botuli-num C2 toxin blocked both random migration of neutrophils and migration induced by FMLP, complement C5a, leuko-triene B4, and a novel monocyte-derived chemotactic agent. The data suggest that botulinum C2 toxin-catalyzed ADP-ri-bosylation of a minor actin pool has a pronounced effect on the activation of human neutrophils by various stimulants