Transepithelial migration of human neutrophils: an in vitro model system.

Abstract

An in vitro model system for studying transepithelial migration of human neutrophils has been developed. Canine kidney epithelial cells grown on micropore filters form a confluent, polarized monolayer with an average transepithelial electrical resistance of 181 ohms.cm2. Neutrophils in a chemotactic chamber are stimulated to undergo random migration, chemokinesis, or chemotaxis through the epithelium. When stimulated by a gradient of the synthetic chemoattractant fMet-Leu-Phe, significantly more neutrophils traverse the low-resistance epithelium than do under conditions of random migration or chemokinesis. Transmission and scanning electron microscopy of this process reveal that neutrophils traverse the epithelium through the intercellular space. After leukocyte emigration, lateral epithelial cell membranes reapproximate. Neutrophils undergoing chemotaxis can also traverse the polarized epithelium from the basal epithelial surface, which suggests that the chemotactic gradient and not the apical-basal polarity of the epithelial cells determines the direction of transepithelial migration. The data further suggest that (i) the in vitro model of leukocyte transepithelial migration morphologically simulates the in vivo process, (ii) neutrophils more readily penetrate the epithelium when attracted by a chemotactic factor, and (iii) neutrophils can traverse a low-resistance epithelium in the absence of serum and connective tissue factors.