Article

Contrasting roles for CXCR2 during experimental colitis.

Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 4N1.
Experimental and Molecular Pathology (impact factor: 2.42). 02/2004; 76(1):1-8. DOI:10.1016/j.yexmp.2003.08.004 pp.1-8
Source: PubMed

ABSTRACT Neutrophil recruitment into the colon is believed to play a crucial pathogenic role in the progression of clinical and experimental inflammatory bowel diseases (IBDs). The chemokine receptor CXCR2 is highly expressed on neutrophils, and promotes neutrophil recruitment in several inflammatory diseases. The present study determined the biological role of CXCR2 during trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat by assessing effects of CXCR2 antibody neutralization on neutrophil accumulation during the early (8 h) and late phase (day 7) of TNBS-induced colitis. CXCR2 expression was elevated (>3-fold above control) within 8 h and remained elevated to day 7 of colitis induction, in parallel with significant increases in neutrophil infiltration. Treatment of colitic rats with a single dose of CXCR2 neutralizing antibody significantly reduced colonic neutrophil accumulation during the early (8 h) phase of TNBS-induced colitis. However, chronic administration of CXCR2 antibody did not reduce colonic neutrophil accumulation during the late phase (day 7) of TNBS-induced colitis. In summary, the present findings suggest a functional role for CXCR2 in initiating neutrophil recruitment during the early phase of TNBS-induced acute colitis, and demonstrate that: early colonic neutrophil accumulation is CXCR2 dependent and the late phase colonic neutrophil accumulation is CXCR2 independent.

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Keywords

biological role
 
chemokine receptor CXCR2
 
colitis induction
 
colonic neutrophil accumulation
 
crucial pathogenic role
 
CXCR2 antibody neutralization
 
CXCR2 expression
 
experimental inflammatory bowel diseases
 
functional role
 
initiating neutrophil recruitment
 
neutrophil accumulation
 
neutrophil infiltration
 
Neutrophil recruitment
 
neutrophils
 
phase colonic neutrophil accumulation
 
promotes neutrophil recruitment
 
TNBS)-induced colitis
 
TNBS-induced acute colitis
 
TNBS-induced colitis
 
trinitrobenzene sulfonic acid