Botulinum C2 toxin ADP-ribosylates actin and enhances O2- 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 botulinum C2 toxin for 45 min increased FMLP-stimulated superoxide anion (O2-) production 1.5-5-fold, whereas only a minor fraction of the cellular actin pool (approximately 20%) was ADP-ribosylated. Effects of botulinum C2 toxin depended on toxin concentrations, presence of both components of the toxin, and incubation time. Cytochalasin B similarly enhanced O2- production. 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-induced release of N-acetyl-glucosaminidase by 100-250%; release of vitamin B12-binding protein induced by FMLP and PMA was enhanced by approximately 150 and 50%, respectively. Botulinum C2 toxin blocked both random migration of neutrophils and migration induced by FMLP, complement C5a, leukotriene B4, and a novel monocyte-derived chemotactic agent. The data suggest that botulinum C2 toxin-catalyzed ADP-ribosylation of a minor actin pool has a pronounced effect on the activation of human neutrophils by various stimulants.
Norgauer
J
J
Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität, Giessen, Federal Republic of Germany.
Kownatzki
E
E
Seifert
R
R
Aktories
K
K
D000118:Acetylglucosaminidase / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins; D001905:Botulinum Toxins / Q000494:pharmacology*; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D029968:Escherichia coli Proteins; D006801:Humans; D016209:Interleukin-8; D026901:Membrane Transport Proteins; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D010100:Oxygen / Q000096:biosynthesis* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D018000:Receptors, Peptide
D000199:Actins; D001425:Bacterial Outer Membrane Proteins; C044592:BtuB protein, E coli; D002630:Chemotactic Factors; D029968:Escherichia coli Proteins; D016209:Interleukin-8; D026901:Membrane Transport Proteins; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D000246:Adenosine Diphosphate Ribose; D000118:Acetylglucosaminidase; D001905:Botulinum Toxins; D010100:Oxygen