Effects of Clostridium difficile toxin B on activation of rat peritoneal mast cells

Clostridium difficile toxin B that inactivates Rho subfamily proteins by glucosylation, inhibited dinitrophenyl-conjugated bovine serum albumin (DNP-BSA) and phorbol 12-myristate 13-acetate (PMA)-induced mast cell activation by 80 to 90% in a concentration- and time dependent manner with a delay of about 30 min. Activation of mast cells by compound 48/80 and calcium ionophore A23187 was maximally inhibited by about 50%. Inhibition by toxin B was observed with suspended, attached and permeabilised mast cells. C3 ADP-ribosyltransferase, which selectively inactivates RhoA,B,C subtype proteins inhibited antigen, compound 48/80, PMA, A23187 and GTP[S]-induced degranulation of permeabilised mast cells. C3-induced inhibition of stimulated histamine release was smaller than that observed with toxin B and both inhibitory effects were not additive. These findings suggest the involvement of Rho subtype GTPases and, additionally, of other members of the Rho subfamily GTPases in activation of rat peritoneal mast cells.