RESPIRATORY SYNCYTIAL VIRUS-INFECTION ENHANCES NEUTROPHIL AND EOSINOPHIL ADHESION TO CULTURED RESPIRATORY EPITHELIAL-CELLS - ROLES OF CD18 AND INTERCELLULAR-ADHESION MOLECULE-1

Respiratory syncytial virus (RSV) infections in children precipitate a cute episodes of respiratory obstruction that are associated with infl ux of inflammatory cells into the airway. Since RSV can induce the exp ression of adhesion molecules, particularly intercellular adhesion mol ecule-1 (ICAM-1), by the respiratory epithelium, the hypothesis has be en proposed that ICAM-1 expression contributes to airway inflammation by supporting adhesion and retention of infiltrating inflammatory leuk ocytes. To test this hypothesis, A549 cells (an immortalized human alv eolar epithelial type II cell-like line) were infected with RSV, and t he ability of these infected monolayers to support adhesion by human n eutrophils (NEUT) and eosinophils (EOS) was measured. RSV infection si gnificantly increased ICAM-1 expression by A549 monolayers (p < 0.001) . Although NEUT adhesion to A549 monolayers was significantly enhanced following RSV infection (p < 0.001), infection alone resulted in litt le change in EOS adherence, However, if EOS were first activated with phorbol ester (PMA), adhesion to both control and RSV-infected A549 ce lls was enhanced, with greater levels of adhesion supported by RSV-inf ected cultures (p < 0.001), The requirement for EOS activation (but no t for NEUT activation) before adhesion remained when NEUT and EOS were prepared and compared from the same donor. Despite this difference, N EUT and EOS adhesion was reduced by blocking Abs to epithelial ICAM-1 or granulocyte CD18 adhesion proteins (p < 0.01), However, only NEUT a dhesion was blocked by Ab to CD11a, Our results show that RSV infectio ns of respiratory epithelial monolayers can promote inflammatory cell adherence which could, in turn, potentially contribute to the airway i njury and obstruction that accompanies bronchiolitis.