Clostridium difficile Toxin A Induces the Release of Neutrophil Chemotactic Factors From Rat Peritoneal Macrophages: Role of Interleukin1b, Tumor Necrosis Factor Alpha, and Leukotrienes (original) (raw)

Clostridium difficile produces a potent enterotoxin and cytotoxin, toxins A and B, respectively, which appear to be responsible for pseudomenbranous colitis and antibiotic-associated diarrhea. In the present study we explored the neutrophil migration evoked by toxin A in the peritoneal cavities and subcutaneous air pouches of rats and examined the role of macrophages and their inflammatory mediators in this process. Toxin A causes a significant dose-dependent neutrophil influx into the peritoneal cavity, with a maximal response at 0.1 g/ml and at 4 h. The depletion of macrophages by peritoneal washing prevents the toxin A-induced neutrophil migration into the peritoneal cavity. In contrast, an increase in macrophages induced by peritoneal injection of thioglycolate amplifies this toxin effect on neutrophil migration. Furthermore, the injection of supernatants from toxin A-stimulated macrophages into the rat peritoneal cavity causes significant neutrophil migration.