Interleukin-5 enhances eosinophil adhesion to bronchial epithelial cells

Background Eosinophil-bronchial epithelial cell interactions are thought to be central to the pathogenesis of asthma, both in terms of the epithelium as a source of pro-inflammatory mediators and as a target for eosinophil-me diated damage. We have therefore investigated adhesion interactions between these two cell types. Objectives To determine the role of eosinophil and epithelial activation on eosinophil adhesion to bronchial epithelium and to characterize the adhesi on receptors mediating eosinophil adhesion. Methods Eosinophils were purified from human peripheral blood by immunomagn etic selection and adhesion to confluent cultures of the airway epithelial cell lines A549 and BEAS-2B was studied. Results Stimulation of A549 cells with TNF alpha, IFN gamma or a combinatio n of 50 ng/mL of TNF alpha, IFN gamma and IL-1 (cytomix) did not effect eos inophil binding despite an increase in ICAM-1 expression. Similarly stimula tion of eosinophils with PAF or IL-5 had no effect on eosinophil binding to medium- or cytokine-treated A549 cells. In contrast stimulation of BEAS-2B cells with cytomix caused a significant increase in eosinophil adhesion. T his was associated with an increase in expression of ICAM-1 and induced exp ression of VCAM-1. Treatment of eosinophils with Mn2+ and IL-5 but not eota xin, RANTES or PAF also significantly enhanced eosinophil adhesion to mediu m-treated BEAS-2B cells. Using blocking mAbs we were able to demonstrate th at the increased adhesion resulting from stimulation of eosinophils or BEAS -2B cells was in both cases mediated by a combination of CD18 and alpha 4 i ntegrins. Conclusions This study demonstrates a selective role for IL-5 in mediating integrin-dependent eosinophil adhesion to airway epithelium and once again emphasizes the importance of this cytokine in controlling eosinophil activa tion in diseases such as asthma.