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RSV infection of human airway epithelial cells causes production of the beta-chemokine RANTES

S. Becker, W. Reed, F. W. Henderson, T. L. Noah
1997 American Journal of Physiology - Lung cellular and Molecular Physiology  
Please cite this article as: Herbert JA, Deng Y, Hardelid P, et al. β2 integrin LFA1 mediates airway damage following neutrophil trans-epithelial migration during RSV infection. Eur Respir J 2020; in press (https://doi. Abstract RSV bronchiolitis is the most common cause of infant hospital admissions, but there is limited understanding of the mechanisms of disease and no specific anti-viral treatment. Using a novel in vitro primary trans-epithelial neutrophil migration model and innovative
more » ... and innovative imaging methods, we show that RSV infection of nasal airway epithelium increased neutrophil trans-epithelial migration and adhesion to infected epithelial cells, which is associated with epithelial cell damage, reduced ciliary beat frequency, but also a reduction in infectious viral load. Following migration, RSV infection results in greater neutrophil activation, degranulation and release of neutrophil elastase into the airway surface media compared to neutrophils that migrated across mock-infected nasal epithelial cells. Blocking of the interaction between the ligand on neutrophils (the β2 integrin LFA-1) for intracellular adhesion molecule-1 (ICAM-1) on epithelial cells reduced neutrophil adherence to RSV infected cells and epithelial cell damage to pre-infection levels, but did not reduce the numbers of neutrophils which migrated or prevent the reduction in infectious viral load. These findings have provided important insights into the contribution of neutrophils to airway damage and viral clearance, which are relevant to pathophysiology of RSV bronchiolitis. This model is a convenient, quantitative pre-clinical model that will further elucidate mechanisms that drive disease severity and has utility in anti-viral drug discovery. Abstract word count 207 (max 250) TITLE: β2 integrin LFA1 mediates airway damage following neutrophil trans-epithelial migration during RSV infection. METHODS AUTHORS AND AFFILIATIONS: A Video Methodology can be found here: PROTOCOL:
doi:10.1152/ajplung.1997.272.3.l512 pmid:9124609 fatcat:7todomvhx5aujkldhpw4u3jtxi