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Clostridium difficile Toxin A Stimulates Macrophage- Inflammatory Protein-2 Production in Rat Intestinal Epithelial Cells

1998; American Association of Immunologists; Volume: 160; Issue: 12 Linguagem: Inglês

10.4049/jimmunol.160.12.6039

1550-6606

Ignazio Castagliuolo, Andrew C. Keates, Chi Chung Wang, Asiya Pasha, Leyla Valenick, Ciarán P. Kelly, Sigfús Nikulásson, J. Thomas LaMont, Charalabos Pothoulakis,

Gastrointestinal motility and disorders

Neutrophil infiltration of the colonic mucosa is a hallmark of Clostridium difficile toxin A-mediated enterocolitis. Macrophage-inflammatory protein-2 (MIP-2) is a potent neutrophil chemoattractant secreted by rat macrophages and epithelial cells in response to inflammatory stimuli. In this work, we report that administration of toxin A into rat ileal loops increased mucosal levels of MIP-2 before the onset of fluid secretion and mucosal neutrophil infiltration. Administration of rabbit anti-MIP-2 IgG, but not control IgG, reduced toxin A-mediated secretion (by 58%), mucosal permeability (by 80%), and myeloperoxidase activity (by 85%). Immunohistochemical analysis demonstrated increased MIP-2 expression in intestinal epithelial and lamina propria cells 1 h after toxin A administration. Intestinal epithelial cells purified from toxin A-exposed ileal loops also showed increased MIP-2 mRNA expression and MIP-2 protein release that was inhibited by pretreatment of rats with the transcriptional inhibitor actinomycin D. These results indicate that C. difficile toxin A induces MIP-2 release from intestinal epithelial cells and that MIP-2 contributes to neutrophil mucosal influx during toxin A enteritis.