The role of CCL3/macrophage inflammatory protein-1alpha in experimental colitis.
CCL3/macrophage inflammatory protein (MIP-1)-1alpha is elevated in the rectal biopsies of patients with active inflammatory bowel diseases, but its role remains undefined. The present study examined the role of CCL3/MIP-1alpha during trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat. Colonic CCL3/MIP-1alpha levels were elevated (>20-fold above control) within 24 h and remained elevated to day 7 of colitis induction by TNBS administration. In addition, significant increases in colonic neutrophil accumulation were observed within 24 h to day 7 of TNBS treatment. Pre-treatment of rats with a single dose of CCL3/MIP-1alpha antibody significantly reduced (47%) colonic neutrophil accumulation during the early (24 h) phase of TNBS-induced colitis. In contrast, chronic (repeated) administration of CCL3/MIP-1alpha antibody did not attenuate colonic neutrophil accumulation during the late phase (day 7) of TNBS-induced colitis. These results suggest a role for CCL3/MIP-1alpha in promoting colonic neutrophil accumulation during the early (24 h) phase of TNBS-induced colitis.
Ajuebor
Maureen N
MN
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1. ajuebor@ucalgary.ca
Kunkel
Steven L
SL
Hogaboam
Cory M
CM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D003106:Colon / Q000473:pathology; D004195:Disease Models, Animal; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D008297:Male; D020556:Neutrophil Infiltration; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
D000906:Antibodies; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D014302:Trinitrobenzenesulfonic Acid