Am. J. Respir. Cell Mol. Biol., Volume 19, Number 3, September, 1998 408-418

A CD18/ICAM-1-dependent Pathway Mediates Eosinophil Adhesion to Human Bronchial Epithelial Cells

Anne Burke-Gaffney and Paul G. Hellewell

Department of Applied Pharmacology, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom

Eosinophil adhesion to airway epithelium is believed to facilitate eosinophil accumulation and retention in asthmatic airways. Monoclonal antibodies (mAb) against intercellular adhesion molecule-1 (ICAM-1) and its CD18 leukocyte integrin ligands have been shown to inhibit airway eosinophilia in animal models of asthma, although the role of this pathway in eosinophil-epithelial adhesion is not fully understood. To investigate the role in vitro of CD18 and ICAM-1, we measured adhesion of fluorescently labeled human eosinophils to normal human bronchial epithelial cell (NHBEC) monolayers pretreated for 24 h with culture medium (low constitutive ICAM-1) or tumor necrosis factor- (TNF-; 1 ng/ml) and interferon- (IFN-) (10 ng/ml; increased ICAM-1). Stimulation of eosinophils with C5a (10⁷ M) increased adhesion measured at 30 min to unactivated NHBEC from 11.4 ± 0.7 to 15.5 ± 0.4% (n = 4), and this increase was CD18/ICAM-1-independent, whereas phorbolmyristate acetate (PMA) (10⁸ M)-induced adhesion (20.7 ± 1.7%) was abolished by anti-CD18 and reduced by anti-ICAM-1. In contrast, C5a- and PMA-induced adhesion to TNF-/IFN--activated NHBEC (increased from 11.1 ± 1.3% to 21.9 ± 1.0% and 27.6 ± 1.9%, respectively) was CD18- and ICAM-1-dependent. Eotaxin, but not regulated on activation normal T cells expressed and secreted, macrophage inflammatory protein-1, formyl methionyl leucyl phenylalanine, leukotriene B₄ or platelet-activating factor, also induced CD18/ICAM-1-dependent adhesion to activated NHBEC. In the absence of added chemoattractants, eosinophil adhesion to NHBEC increased with time and, at 120 min, was significantly greater (P < 0.01) to activated NHBEC (37.3 ± 2.4%, n = 5) than to unactivated monolayers (24.3 ± 1.9%); mAb against CD18 or ICAM-1 abolished increased, but not basal, adhesion. These results suggest that CD18/ICAM-1 mediated eosinophil adhesion to activated NHBEC but that adhesion to resting NHBEC was largely independent of this pathway.

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