STIMULATION OF BOTH HUMAN BRONCHIAL EPITHELIUM AND NEUTROPHILS IS NEEDED FOR MAXIMAL INTERACTIVE ADHESION

It has become clear that the bronchial epithelium is not just a passiv e barrier but plays an active role in inflammation. It can produce sev eral inflammatory mediators and does express cell adhesion molecules o f which intercellular adhesion molecule (ICAM)-1 can be upregulated by cytokines like interferon (IFN)-gamma. In the present study, we analy zed in detail the interaction of neutrophils with human bronchial epit helial cells, both primary cultured cells and the bronchial epithelial cell line BEAS-2B. Confluent monolayers of epithelial cells were incu bated with freshly isolated Cr-51-labeled neutrophils for 30 min at 37 degrees C; then the nonadherent cells were removed by washing gently. Stimulation of the epithelial cells with IFN-gamma or the combination of IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) (which doubl es the ICAM-1 expression) increased neutrophil adhesion. Activation of the neutrophils themselves with N-formylmethionyl-leucyl-phenylalanin e (fMLP), platelet-activating factor, or TNF-alpha also caused a profo und enhancement of the adhesion. A significant additional increase was found when the epithelial cells had been exposed to IFN-gamma and the neutrophils were stimulated with fMLP simultaneously. This effect was even more pronounced with epithelium preincubated with IFN-gamma and TNF-alpha. With the use of monoclonal antibodies against CD18 and ICAM -1, it was demonstrated that the increased adhesion was mainly mediate d by the ICAM-1/beta(2)-integrin interaction. This study highlights th at both the activation state of the bronchial epithelial cells and the activation state of the neutrophils are critical for their interactiv e adhesion.