ICAM-1-independent, CD18-dependent adhesion between neutrophils and human airway epithelial cells exposed in vitro to...

Inhalant exposure to ozone can cause diffuse airway epithelial injury that is associated with an inflammatory response, including the influx of neutrophils into lung and airway tissue. We have previously documented enhanced adhesiveness by neutrophils for human airway epithelial cells in in vitro models of diseases associated with airway inflammation and have suggested that this enhanced adhesion may contribute to neutrophil-mediated airway injury. When primary human tracheal epithelial cell (TEC) monolayers were exposed to ozone at 2.0 ppm for 30 min or 0.5 ppm for 2 h, the percentage of PMN adhering to these cells increased from < 5% to a maximum of approximately 75% by 18 to 24 h after the ozone exposure. No change was observed within the first 2 h after ozone exposure, but there was a statistically significant increase in PMN adhesion by 8 h after exposure. In contrast to previous studies with cytokine exposure or respiratory virus infection of TEC, the increased adhesion after ozone exposure was not associated with an increase in epithelial expression of ICAM-1. Consistent with the lack of induction of ICAM-1 by ozone exposure was the observation that anti-ICAM-1 mAbs (mAb; R6.5) previously shown to block PMN adhesion to TEC with increased ICAM-1 expression had no effect on PMN adhesion to ozone-exposed TEC. However, mAbs against CD11b or CD18 on PMN blocked PMN adhesion to ozone-exposed TEC by approximately 55 and 80%, respectively. Chemoattractant preactivation of PMN (e.g., with 10 nM FMLP) was necessary to achieve the highest levels of adhesion to ozone-treated TEC, in marked contrast to our earlier studies with PMN adhesion to cytokine-treated or virus-infected TEC in which resting and prestimulated PMN exhibited the same high levels of adhesion. We conclude that exposure of human TEC in vitro to ozone results in markedly increased adhesiveness for neutrophils that is caused by the induction of as yet uncharacterized epithelial cell adhesion molecules other than ICAM-1 that function as counterreceptors for the CD11/CD18 integrins on PMN. Maximal PMN adhesiveness to ozone-exposed TEC in this system requires preactivation of the PMN, e.g., with FMLP, suggesting important differences in the way PMN interact with ozone-treated vs cytokine-treated or virus-infected TEC.