C5a plays a role in PMN infiltration into the DSS inflamed colonic mucosa

A role for complement in colitis has been implicated yet it is unclear whether it promotes or possibly inhibits inflammation. As C5a is a potent PMN chemoattractant and PMN infiltrate the mucosa during dextran sulphate sodium (DSS) colitis, we hypothesized that C5aR−/− mice would experience less colitis due to reduced PMN infiltration. Balb/c and C5aR−/− mice were fed 5% DSS in their drinking water for 5 days then were euthanised on day 6 and their colons examined. Balb/c mice experienced limited clinical illness. Their mid‐colons were inflamed with PMN infiltrates in the mucosa, crypt loss, and small focal ulcers. In contrast, C5aR−/− mice experienced a more severe colitis, with greater ulcers, but interestingly PMN remained primarily in the submucosa. Staining for F4/80 indicated that a substantially greater number of macrophages infiltrated the C5aR−/− colon versus the Balb/c mice. In order to rule‐out the possibility that PMN were damaging the colon from the submucosa, C5aR−/− mice receiving DSS were made neutropenic using injections of Gr‐1 antibody. Despite abolishing PMN infiltration, these mice still demonstrated high numbers of mucosal F4/80+ cells and colon damage. Thus while C5a does play a role in PMN recruitment into the mucosa, our hypothesis was incorrect and C5aR−/− mice in fact experience heightened colitis, with macrophages possibly mediating the inflammation. Supported by the CCFC.