Leukocyte-epithelial interactions and mucosal homeostasis

Many common inflammatory disorders are characterized by the infiltration of neutrophils across epithelial lined (mucosal) surfaces resulting in disruption of critical barrier function that protects from microbes and noxious agents. In such conditions, disease symptoms are complex but directly related to leukocyte effects on the barrier and epithelial cell function. It is now highly regarded that cellular factors such as cytokines and receptor-ligand interactions mediating adhesion of leukocytes to epithelial cells have potent effects on epithelial homeostasis, defined by coordinated proliferation, migration, differentiation, and regulated cell shedding. Certain cytokines, for example, not only alter leukocyte interactions with epithelia through changes in expression of adhesion molecules but also affect barrier function through alterations in the composition and dynamics of intercellular junctions. In particular, inflammation-induced loss of many tight junction molecules, in part, can account for dysregulated cellular proliferation, migration, survival, and barrier function. This review will highlight how neutrophils interact with epithelial cells with particular focus on adhesion molecules involved and signaling events that play roles in regulating mucosal homeostasis and pathobiology. A better understanding of these molecular events may provide new ideas for therapeutics directed at attenuating consequences of pathologic inflammation of mucosal surfaces.