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023 A ROLE FOR C5a IN THE RECRUITMENT OF POLYMORPHO-NUCLEAR NEUTROPHILS IN THE DSS INFLAMED COLON R Rostom1,3, R Stillie1,3, KL Roth1, AW Stadnyk1,2,3 Dextran sulphate sodium (DSS) colitis in mice models aspects of human inflammatory bowel disease (IBD), and like IBD, a hallmark is the infiltration of polymorphonuclear neutrophils (PMN) into the inflamed colon. Yet the mechanism by which PMN infiltrate the diseased colon is not understood. The complement cleavage product C5a is a well known PMN chemoattractant and may be involved in recruiting and activating PMN in the inflamed colon. To elucidate the role of C5a in PMN recruitment during DSS colitis, Balb/c and C5a receptor gene knockout (C5aR-/-) mice on Balb/c background were administered 5% DSS in their drinking water for 5 days then killed on day 6. Clinical disease was assessed over the period of DSS and pathology assessed macroscopically and microscopically. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure chemokine mRNA levels in mucosal samples. Control C5aR-/- mice were healthy and their colons uninflamed. Following DSS, C5aR-/- mice lost weight and developed severe rectal bleeding, and their colon lengths were as much as 75% shorter than control inflamed Balb/c mice. Microscopic assessment revealed the presence of a cellular infiltrate, edema and crypt damage in both strains in inflamed mice; however, at day 6 only C5aR-/- mice had ulcers. Both strains showed increases in CXCL2 mRNA in their mucosa yet surprisingly, there were fewer PMN in the infiltrate in C5aR-/- mice compared to Balb/c mice. In addition, C5aR-/- mice expressed significantly less iNOS mRNA than the Balb/c mice. While C5aR-/- experience more severe colitis than Balb/c mice, these data support the conclusion that C5a does play a role in PMN recruitment into the colon.
Departments of 1Microbiology and Immunology and 2Pediatrics, Dalhousie University; 3Dalhousie Inflammation Group, Halifax, Nova Scotia
This research is funded by the Crohn's and Colitis Foundation of Canada