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Am J Physiol Lung Cell Mol Physiol 270: L80-L87, 1996;
1040-0605/96 $5.00
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AJP - Lung Cellular and Molecular Physiology, Vol 270, Issue 1 80-L87, Copyright © 1996 by American Physiological Society

ARTICLES

Stimulation of both human bronchial epithelium and neutrophils is needed for maximal interactive adhesion

P. G. Bloemen, M. C. Van den Tweel, P. A. Henricks, F. Engels, M. J. Van de Velde, F. J. Blomjous and F. P. Nijkamp
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.

It has become clear that the bronchial epithelium is not just a passive barrier but plays an active role in inflammation. It can produce several inflammatory mediators and does express cell adhesion molecules of which intercellular adhesion molecule (ICAM)-1 can be upregulated by cytokines like interferon (IFN)-gamma. In the present study, we analyzed in detail the interaction of neutrophils with human bronchial epithelial cells, both primary cultured cells and the bronchial epithelial cell line BEAS-2B. Confluent monolayers of epithelial cells were incubated with freshly isolated 51Cr-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 doubles the ICAM-1 expression) increased neutrophil adhesion. Activation of the neutrophils themselves with N-formylmethionyl-leucyl-phenylalanine (fMLP), platelet-activating factor, or TNF-alpha also caused a profound 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 mediated by the ICAM-1/beta 2-integrin interaction. This study highlights that both the activation state of the bronchial epithelial cells and the activation state of the neutrophils are critical for their interactive adhesion.


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