Neutrophil (PMN) infiltration of the intestinal mucosa and accumulation in the intestinal lumen is a hallmark of Inflammatory Bowel Diseases (IBD). While en masse migration of PMNs across epithelial layers is often associated with epithelial injury, the function of transmigrated PMNs in the intestinal lumen, their interactions with luminal epithelial receptors and the consequent effects on epithelial homeostasis is unclear. Thus, ongoing studies in our laboratory are aimed at elucidating the mechanisms governing PMN-induced epithelial injury and alterations in epithelial barrier function. Our recent findings identified ICAM-1 as an important mediator of PMN retention and accumulation in the intestinal lumen and regulator of epithelial permeability and mucosal healing. Furthermore, recent evidence suggests that the interactions between PMNs and resident macrophages (including perivascular and crypt macrophages, PVMs and RCMs, respectively) may contribute to trafficking of these cells and the regulation of intestinal homeostasis. Thus, we are interested in defining PMN tissue interactions with resident macrophages and luminal interactions with epithelial cells in models of IBD and mucosal injury.