Inflammatory responses in the intestinal mucosa inevitably result in the recruitment of neutrophils (polymorphonuclear leukocytes [PMNs]). Epithelial cells that line the mucosa play an integral role in the recruitment, maintenance, and clearance of PMNs at sites of inflammation. The consequences of such PMN-epithelial interactions often determine tissue responses and, ultimately, organ function. For this reason, there is significant interest in understanding how PMNs function in the mucosa during inflammation. Recent studies have shown that PMNs play a more significant role in molding of the immune response than previously thought. Here, we review the recent literature regarding the contribution of PMNs to the development and resolution of inflammation, with an emphasis on the role of the tissue microenvironment and pathways for promoting epithelial restitution. These studies highlight the complex nature of inflammatory pathways and provide important insight into the difficulties of treating mucosal inflammation.
Keywords: ATP, adenosine triphosphatase; CGD, chronic granulomatous disease; DMOG, dimethyloxalylglycine; Epithelium; GI, gastrointestinal; HIF, hypoxia-inducible factor; Hypoxia-Inducible Factor; IBD, inflammatory bowel disease; ICAM-1, intracellular adhesion molecule-1; IL, interleukin; Inflammation; Metabolism; Microbiota; NADPH, reduced nicotinamide adenine dinucleotide phosphate; PHD, prolyl-hydroxylase; PMN, polymorphonuclear leukocyte; SIRPα, signal-regulatory protein-α.