RESPIRATORY SYNCYTIAL VIRUS-INFECTED PULMONARY EPITHELIAL-CELLS INDUCE EOSINOPHIL DEGRANULATION BY A CD18-MEDIATED MECHANISM

Respiratory syncytial virus (RSV)-induced bronchiolitis in infants is characterized by wheezing, respiratory distress, and the histologic fi ndings of necrosis and sloughing of airway epithelium. High concentrat ions of eosinophil cationic protein (ECP), a cytotoxic protein contain ed in the granules of eosinophils, have been found in the airways of R SV-infected infants. The mechanisms of eosinophil degranulation in viv o remain largely unknown. Since RSV-infected respiratory epithelial ce lls are a rich source of cytokines with eosinophil-activating properti es, our studies were designed to mimic in vitro the interaction betwee n RSV, pulmonary epithelial cells (A549), and eosinophils in the airwa y mucosa, We report in this work that, in the absence of epithelial ce lls, neither RSV, in the form of purified virions, nor UV-irradiated c ulture supernatant of RSV-infected epithelial cells (RSV-CM) induced e osinophil degranulation, On the other hand, eosinophils released signi ficant amount of ECP when cultured with RSV-infected A549 cells. Uninf ected A549 cells, which failed to induce eosinophil degranulation, wer e equally effective in triggering ECP release if they were cultured wi th eosinophils in the presence of RSV-CM, Although RSV-CM induced the up-regulation of the beta(2) integrin CD11b on eosinophils and the exp ression of ICAM-1 on A549 cells, release of ECP was inhibited signific antly by anti-CD18 mAb, but not by anti-ICAM-1 mAb, These results sugg est a novel mechanism by which respiratory viruses may trigger the det rimental release of eosinophil granule proteins in the airway mucosa.