β 2 -integrin LFA1 mediates airway damage following neutrophil transepithelial migration during respiratory syncytial virus infection.

Autor: Herbert JA; UCL Great Ormond Street Institute of Child Health, London, UK., Deng Y; UCL Great Ormond Street Institute of Child Health, London, UK.; Dept of Respiratory Medical Centre, Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China., Hardelid P; UCL Great Ormond Street Institute of Child Health, London, UK., Robinson E; UCL Great Ormond Street Institute of Child Health, London, UK., Ren L; UCL Great Ormond Street Institute of Child Health, London, UK.; Dept of Respiratory Medical Centre, Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China., Moulding D; UCL Great Ormond Street Institute of Child Health, London, UK., Smyth RL; UCL Great Ormond Street Institute of Child Health, London, UK.; Joint senior author., Smith CM; UCL Great Ormond Street Institute of Child Health, London, UK c.m.smith@ucl.ac.uk.; Joint senior author.
Jazyk: angličtina
Zdroj: The European respiratory journal [Eur Respir J] 2020 Aug 06; Vol. 56 (2). Date of Electronic Publication: 2020 Aug 06 (Print Publication: 2020).
DOI: 10.1183/13993003.02216-2019
Abstrakt: Respiratory syncytial virus (RSV) bronchiolitis is the most common cause of infant hospital admissions, but there is limited understanding of the mechanisms of disease, and no specific antiviral treatment. Using a novel in vitro primary transepithelial neutrophil migration model and innovative imaging methods, we show that RSV infection of nasal airway epithelium increased neutrophil transepithelial migration and adhesion to infected epithelial cells, which is associated with epithelial cell damage and reduced ciliary beat frequency, but also with 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 β 2 -integrin LFA-1) for intracellular adhesion molecule (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 that 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 the pathophysiology of RSV bronchiolitis. This model is a convenient, quantitative preclinical model that will further elucidate mechanisms that drive disease severity and has utility in antiviral drug discovery.
Competing Interests: Conflict of interest: J.A. Herbert has nothing to disclose. Conflict of interest: Y. Deng has nothing to disclose. Conflict of interest: P. Hardelid has nothing to disclose. Conflict of interest: E. Robinson has nothing to disclose. Conflict of interest: L. Ren has nothing to disclose. Conflict of interest: D. Moulding has nothing to disclose. Conflict of interest: R.L. Smyth has nothing to disclose. Conflict of interest: C.M. Smith has nothing to disclose.
(Copyright ©ERS 2020.)
Databáze: MEDLINE
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