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.

Impact of Bronchial Epithelium on Dendritic Cell Migration and Function: Modulation by the Bacterial Motif KpOmpA

“…Moreover, ICAM-1 neutralization on BEC strongly reduced the effect of bronchial epithelium on CCL17 and CCL22 secretion and on the phenotype of recruited MDDC. This suggests that ICAM-1/LFA-1 interactions between BEC and DC precursors are involved in DC activation as well as in the subsequent recruitment of T cells and eosinophils (32). Local administration of KpOmpA in the experimental model also shows that this PAMP induces the recruitment of myeloid DC and the production of CCL20 by BEC in vivo.…”

Eosinophils and CCR3 Regulate Interleukin-13 Transgene-Induced Pulmonary Remodeling

“…Further studies are needed to identify the downstream mechanism, such as alteration in adhesion molecules on resident lung cells by the eotaxin chemokines, in the cooperative orchestration of eosinophil localization in the asthmatic lung. 39,40 Because lung tissue eosinophilia was only partially eotaxin-1-dependent and was independent of eotaxin-2 expression, other CCR3 ligands must contribute to the peribronchial eosinophil accumulation. Taken together, these results support an essential role for CCR3 signaling in orchestrating IL-13-mediated leukocyte recruitment and spatial localization into the lung.…”

Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33: implications for allergic inflammation

“…In addition, an ICAM-1/CD18 interaction was found to initiate firm eosinophil adhesion to bronchial epithelial cells. 31 Despite the high expression of ICAM-3 on resting stage human eosinophils, an anti-inflammatory role of ICAM-3 in inducing apoptosis of eosinophils has been suggested. 32 The switch to enhanced ICAM-1 and reduced ICAM-3 expression on activated eosinophils upon IL-33 stimulation may favor the initiation of proinflammatory responses.…”