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

被引:29
作者
Morteau, O
Castagliuolo, I
Mykoniatis, A
Zacks, J
Wlk, M
Lu, B
Pothoulakis, C [1 ]
Gerard, NP
Gerard, C
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Div Pulm Med, Perimutter Lab,Childrens Hosp, Boston, MA 02215 USA
[3] Boston Univ, Sch Med, Mallory Inst Pathol, Boston, MA 02118 USA
关键词
D O I
10.1053/gast.2002.31873
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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)-1alpha(-/-) 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 < 0.05) increase in ileal fluid accumulation, epithelial damage, and neutrophil infiltration, with all parameters being significantly (P < 0.01) lower in CCR1(-/-) and MIP-1alpha(-/-) mice. Ileal messenger RNA expression of the CCR:1 ligands MIP-1alpha and RANTES and RANTES synthesis were increased in toxin A-treated wild-type mice. The RANTES antagonist Met-RANTES significantly (P < 0.01) reduced the toxin A-induced increases in ileal fluid accumulation and myeloperoxidase activity in wild-type mice. Conclusions: C. difficile toxin A-induced murine enteritis involves CCR1 and its ligands MIP-1alpha and RANTES, which may be important mediators of the neutrophil recruitment characterizing acute, enterotoxin-mediated enteritis.
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页码:725 / 733
页数:9
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