Effect of Clostridium difficile toxin B on IgE receptor-mediated signal transduction in rat basophilic leukemia cells: inhibition of phospholipase D activation.
Antigen (Ag)-stimulated phospholipase D (PLD) activation and secretion were almost abolished by pretreatment of rat basophilic leukemia (RBL)-2H3 cells for 4 h with 5 ng/ml Clostridium difficile Toxin B which is known to inhibit Rho family proteins (Rho, Cdc42, Rac). The concentration-dependent inhibition of PLD activation was well correlated with the level of glucosylation of Rho family proteins. In streptolysin O-permeabilized RBL cells, Toxin B suppressed [3H] phosphatidylbutanol (PBut) formation in response to guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and phorbol 12-myristate 13-acetate (PMA) by 67 and 43%, respectively. The synergistic PLD activation by GTP gamma S and PMA was also reduced by Toxin B by 67%. These results suggest that the IgE receptor-coupled PLD activation is largely mediated by Rho proteins.
Ojio
K
K
Department of Otolaryngology, Gifu University School of Medicine, Japan.
Banno
Y
Y
Nakashima
S
S
Kato
N
N
Watanabe
K
K
Lyerly
D M
DM
Miyata
H
H
Nozawa
Y
Y
D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability; D016360:Clostridioides difficile; D003603:Cytotoxins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020404:Glycerophospholipids; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017455:Receptors, IgE / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013301:Streptolysins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D020404:Glycerophospholipids; D010712:Phosphatidic Acids; D017455:Receptors, IgE; D013301:Streptolysins; C068564:phosphatidylbutanol; C025964:streptolysin O; C031815:toxB protein, Clostridium difficile; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate