Clostridium perfringens alpha-toxin induces rabbit neutrophil adhesion.

Abstract

Clostridium perfringens alpha-toxin, which is one of the main agents involved in the development of gas gangrene, stimulates O(2)(-)production in neutrophils. Exposure of rabbit neutrophils to the alpha-toxin induced firm adhesion of the cells to fibrinogen and fibronectin. Incubation of rabbit neutrophils and neutrophil lysates with alpha-toxin led to the production of diacylglycerol (DG) and L-alpha-phosphatidic acid (PA), respectively. The toxin-induced DG and PA formation preceded the toxin-induced adhesion of the neutrophils to fibrinogen and fibronectin, and the production of O(2)(-). Pertussis toxin inhibited the alpha-toxin-induced formation of PA, the adhesion of the neutrophils to fibrinogen and production. GTP gamma S stimulated the events induced by the alpha-toxin, whereas GDP beta S inhibited them. The alpha-toxin stimulated phosphorylation of a protein with a molecular mass of about 40 kDa. In addition, treatment of the cells with 1-oleoyl-2-acetyl-sn-glycerol (OAG) and phorbol-12,13-dibutyrate (PDBu) stimulated cell adhesion, production of and phosphorylation of the 40 kDa protein, but had no effect on the formation of PA. The events induced by the presence of OAG and PDBu were not inhibited by pertussis toxin. Protein kinase C inhibitors, H-7, staurosporine and chelerythrine, blocked alpha-toxin-induced adhesion, production of O(2)(-)and phosphorylation of the 40 kDa protein. These observations suggested that alpha-toxin-stimulated adhesion to the matrix and production were due to the formation of DG, through activation of phospholipid metabolism by a pertussis-toxin-sensitive GTP-binding protein, followed by activation of protein kinase C by DG.

• Authors: Sadayuki Ochi, Toshihumi Miyawaki, Hisaaki Matsuda, Masataka Oda, Masahiro Nagahama, Jun Sakurai
• Journal: Microbiology (Reading, England) (Microbiology (Reading)) Vol. 148 Issue Pt 1 Pg. 237-45 (Jan 2002) ISSN: 1350-0872 [Print] England
• PMID: 11782516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Toxins
• Calcium-Binding Proteins
• Diglycerides
• Phosphatidic Acids
• Virulence Factors, Bordetella
• guanosine 5'-O-(1-thiotriphosphate)
• Guanosine 5'-O-(3-Thiotriphosphate)
• Fibrinogen
• Pertussis Toxin
• Protein Kinase C
• Type C Phospholipases
• alpha toxin, Clostridium perfringens

Topics

• Animals
• Bacterial Toxins (toxicity)
• Calcium-Binding Proteins
• Cell Adhesion (drug effects)
• Clostridium perfringens (metabolism, pathogenicity)
• Diglycerides (metabolism)
• Fibrinogen (physiology)
• Gas Gangrene (microbiology, physiopathology)
• Guanosine 5'-O-(3-Thiotriphosphate) (analogs & derivatives, pharmacology)
• Neutrophils (drug effects, physiology)
• Pertussis Toxin
• Phosphatidic Acids (metabolism)
• Protein Kinase C (metabolism)
• Rabbits
• Type C Phospholipases (toxicity)
• Virulence Factors, Bordetella (pharmacology)