title: A CD18/ICAM-1-dependent pathway mediates eosinophil adhesion to human bronchial epithelial cells.
abstract: 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-alpha (TNF-alpha; 1 ng/ml) and interferon-gamma (IFN-gamma) (10 ng/ml; increased ICAM-1). Stimulation of eosinophils with C5a (10(-7) 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) (10(-8) 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-alpha/IFN-gamma-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.
authors.affiliation: Department of Applied Pharmacology, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom. a.burke-gaffney@ic.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Burke-Gaffney
authors.forename: P G
authors.initials: PG
authors.lastname: Hellewell
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects*; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC; D015936:Complement C5a / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004804:Eosinophils / Q000502:physiology*; D004847:Epithelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D007975:Leukotriene B4 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; C515456:CCL11 protein, human; D018821:CD18 Antigens; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate