ADHESION OF ACTIVATED EOSINOPHILS TO RESPIRATORY EPITHELIAL-CELLS IS ENHANCED BY TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA

Eosinophilic infiltration and damage to airway epithelium are characte ristic features of asthma. To assess possible interactions between eos inophils and airway epithelium, Percoll-purified human peripheral bloo d eosinophils were evaluated for their ability to adhere to respirator y epithelial cell (REC) cultures. REC (an immortalized cell line, A549 , and primary bronchial epithelial cells) were grown in 96-well tissue culture plates, treated with proinflammatory cytokines (TNF-alpha or IL-1 beta), and eosinophil adhesion to these tissues was determined. C ytokine treatment of the REC cultures significantly increased expressi on of intercellular adhesion molecule-1 (ICAM-1) (P < 0.01). Eosinophi ls demonstrated a variable baseline adhesion to untreated REC which wa s then significantly increased following activation with phorbol myris tate acetate (PMA) (P < 0.01). Furthermore, treatment of REC monolayer s with TNF-alpha or IL-1 beta significantly increased adhesion of PMA- stimulated eosinophils (P < 0.01). To delineate the adhesion proteins involved in the cell-cell interactions, assays were performed in the p resence of specific blocking monoclonal antibodies to eosinophil CD18, CD11a, or CD11b, and REC ICAM-1 molecules. Blocking antibodies to ICA M-1 had no significant effect on levels of eosinophil adhesion. In con trast, antibodies to CD18, CD11a, and CD11b significantly decreased (P < 0.01) eosinophil adhesion, thus demonstrating pivotal roles for the CD11/CD18 (Pt) integrins, but not necessarily for ICAM-1, in interact ions between the REC and eosinophils. These data demonstrate that TNF- alpha and IL-1 beta increase eosinophil adhesion to human respiratory epithelial cell cultures by induction of ligands recognized by eosinop hil beta(2) integrins.