Previous studies have shown that RSV infection of the lower airway results in migration of PMNs into the airway lumen, the mechanisms of which are unknown. We have shown that RSV-infected human alveolar epithelial cells(A549) release IL-8, and express ICAM-1, but their functional roles in PMN migration have not been evaluated. In the current study, the role of IL-8 and ICAM-1 in adhesion and transepithelial migration of PMNs during RSV infection was investigated using A549 monolayers grown on cell culture inserts. 24 h after incubation with purified RSV, sham infection (uninfected control), or tumor necrosis factor-α (TNF-α; positive control to induce IL-8). 10 μg of neutralizing antibodies (Abs) against IL-8, ICAM-1, or control Ab were mixed in the chamber above the monolayer and incubated for 2 h. 1.5× 106 human PMNs were then inoculated into the upper chamber. 3 h later, the PMNs in the top and bottom chambers, and the fraction adherent to A549 monolayers were isolated and quantitated by manual counting. The mean results of triplicate experiments showed that RSV and TNF-α significantly increased PMN adhesion to and migration through A549 monolayers by 259% and 161%, respectively (p < 0.005), when compared with sham(control). Antibody blocking data are: Table

Table 1
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IL-8 and ICAM-1 antibodies completely blocked the adhesion and migration of PMNs during RSV infection (p <0.005). In conclusion, the increased PMN adherence to and migration through alveolar epithelial cells during RSV infection are primarily mediated by IL-8 and ICAM-1. IL-8 may provide the chemotactic gradient and increase the expression of PMN adhesion molecule: Mac-1, while e [Illegible Text] may interact with its ligand Mac-1 on PMNs.