MOLECULAR EVENTS IN NEUTROPHIL TRANSEPITHELIAL MIGRATION

Neutrophil transepithelial migration is a central component of many in flammatory diseases of the gastrointestinal, respiratory and urinary t racts, and correlates with disease symptoms. In vitro modeling with po larized intestinal epithelial monolayers has shown that neutrophil tra nsepithelial migration can influence crucial epithelial functions, ran ging from barrier maintenance to electrolyte secretion. Studies have a lso demonstrated a dynamic involvement of the epithelium in modulating neutrophil transepithelial migration. Characterization of the molecul ar interactions between neutrophils and epithelial cells has revealed that transepithelial migration is dependent on the neutrophil beta(2) integrin CD11b/CD18, and does not appear to involve adhesive interacti ons with the selectins or intercellular adhesion molecule-1. Recent st udies have implicated another transmembrane glycoprotein, CD47, as a c rucial component of the transepithelial migration response. While the precise function of CD47 is not known, current evidence suggests that CD47-dependent events occur after CD11b/CD18-mediated neutrophil adhes ion to the epithelium. This review will highlight key features of the current understanding of the molecular events important in neutrophil migration across epithelial surfaces.