FPR1 does not mediate neutrophil infiltration in experimental colitis

Abstract

One hallmark of the inflammatory bowel diseases is the infiltration of neutrophils (PMN) into the mucosa. The mechanism behind this infiltration is unclear but bacterial N‐formyl peptides are candidates since these are potent chemoattractants and activating factors for PMN. We investigated this hypothesis by inducing colitis in mice deficient for the formyl peptide receptor, FPR1. FPR1‐/‐ and wild type (WT) mice were administered dextran sodium sulphate (DSS) through their drinking water for 5 days followed by one day of pure water (acute phase) or 4 days of water (recovery phase), or for 2 DSS cycles (chronic phase) with the second cycle commencing on day 22. During acute colitis FPR1‐/‐ mice lost up to 5% of their starting body weight whereas WT mice lost up to 20%. However, the histopathology was similar between the two groups at both the acute and recovery phase points. This included ulcers, PMN infiltration, and loss of crypt architecture. In contrast, during the chronic phase FPR1‐/‐ mice experienced weight loss of up to 20%, greater clinical illness, and 15% shorter colons than WT mice, all indications of a more severe disease. Whether this is reflected in differences in the histopathology remains to be evaluated. We conclude that FPR1 is not necessary for PMN infiltration into the acutely inflamed colon; however, it may play a role in chronic colitis. Funded by the CCFC and an IWK Health Centre Fellowship to SMF.