Genetic deficiency in the chemokine receptor CCR1 protects against acute clostridium difficile toxin A enteritis in mice

Abstract Background & Aims: The role of the CC chemokine receptor (CCR) 1 in acute enteritis was investigated by subjecting CCR1 knockout mice to Clostridium difficile toxin A treatment. Methods: Toxin A or vehicle was injected into ileal loops in anesthetized wild-type, CCR1-/- and macrophage inhibitory protein (MIP)-1α −/− mice. After 1–4 hours, fluid accumulation was calculated, and the loops were processed for histology, myeloperoxidase activity, regulated on activation, normal T cell expressed and secreted (RANTES) production, and messenger RNA measurements. Results: Toxin A induced in all mice a significant ( P P −/− and MIP-1α −/− mice. Ileal messenger RNA expression of the CCR1 ligands MIP-1α and RANTES and RANTES synthesis were increased in toxin A–treated wild-type mice. The RANTES antagonist Met-RANTES significantly ( P Conclusions: C. difficile toxin A–induced murine enteritis involves CCR1 and its ligands MIP-1α and RANTES, which may be important mediators of the neutrophil recruitment characterizing acute, enterotoxin-mediated enteritis. GASTROENTEROLOGY 2002;122:725-733