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 findings of necrosis and sloughing of airway epithelium. High concentrations of eosinophil cationic protein (ECP), a cytotoxic protein contained in the granules of eosinophils, have been found in the airways of RSV-infected infants. The mechanisms of eosinophil degranulation in vivo remain largely unknown. Since RSV-infected respiratory epithelial cells are a rich source of cytokines with eosinophil-activating properties, our studies were designed to mimic in vitro the interaction between RSV, pulmonary epithelial cells (A549), and eosinophils in the airway mucosa. We report in this work that, in the absence of epithelial cells, neither RSV, in the form of purified virions, nor UV-irradiated culture supernatant of RSV-infected epithelial cells (RSV-CM) induced eosinophil degranulation. On the other hand, eosinophils released significant amount of ECP when cultured with RSV-infected A549 cells. Uninfected A549 cells, which failed to induce eosinophil degranulation, were equally effective in triggering ECP release if they were cultured with eosinophils in the presence of RSV-CM. Although RSV-CM induced the up-regulation of the beta2 integrin CD11b on eosinophils and the expression of ICAM-1 on A549 cells, release of ECP was inhibited significantly by anti-CD18 mAb, but not by anti-ICAM-1 mAb. These results suggest a novel mechanism by which respiratory viruses may trigger the detrimental release of eosinophil granule proteins in the airway mucosa.
Olszewska-Pazdrak
B
B
Department of Pediatrics, The University of Texas Medical Branch, Galveston 77555, USA.
Pazdrak
K
K
Ogra
P L
PL
Garofalo
R P
RP
D001798:Blood Proteins / Q000378:metabolism; D018845:CD11 Antigens / Q000032:analysis; D018821:CD18 Antigens / Q000502:physiology*; D015550:Cell Degranulation; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000502:physiology*; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology; D008168:Lung / Q000276:immunology* / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000502:physiology*; D012260:Ribonucleases
D001798:Blood Proteins; D018845:CD11 Antigens; D018821:CD18 Antigens; D047091:Eosinophil Granule Proteins; D018799:Intercellular Adhesion Molecule-1; D012260:Ribonucleases