INDUCTION OF ICAM-1 EXPRESSION ON HUMAN AIRWAY EPITHELIAL-CELLS BY INFLAMMATORY CYTOKINES - EFFECTS ON NEUTROPHIL-EPITHELIAL CELL-ADHESION

Inflammation of the human airways in diseases such as chronic bronchitis, cystic fibrosis with Pseudomonas endobronchial infection, and possibly asthma during late-phase reactions involves a local influx of neutrophils (PMN) that may participate in airway epithelial injury. PMN-mediated cellular injury is most efficient under conditions of PMN-target cell adhesion. PMN express adhesive glycoproteins of the CD11/CD18 family that are counter-receptors for intercellular adhesion molecule-I (ICAM-1), found on various cell types. We proposed that adherence by PMN to human airway epithelial cells via ICAM-1 might be an important mechanism in inflammatory airway diseases. We found that although PMN adhere poorly (< 5%) to monolayers of human tracheal epithelial cells (TEC) in primary culture, they adhere readily (45 to 50%) to an SV40-immortalized line of human TEC, designated 9HTEo-. We also found 6-fold greater surface expression of ICAM4 on 9HTEo- compared with primary TEC. Blocking surface ICAM4 on 9HTEo- cells with specific monoclonal antibody inhibited PMN adherence by about 50%. Thus, ICAM4 plays a major role in this adherence, although it is possible that other epithelial ligands contribute also. Antibodies to CD11a, CD11b, and CD18 on PMN also inhibited PMN-epithelial adherence. Treatment of primary TEC monolayers with the proinflammatory cytokines interleukin-I (IL-1) or tumor necrosis factor-alpha (TNF-alpha) caused a 3- to 4-fold increase in both cell surface ICAM4 expression and support of PMN adhesion. Treatment of full-thickness tracheal explants with IL-1 or TNF-alpha markedly increased the surface expression of ICAM4 on most of the epithelial cells, as determined by immunohistochemistry. These findings suggest a role for ICAM-1-dependent PMN-epithelial cell adhesion in the pathophysiology of inflammatory airway diseases.