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Transepithelial exit of leucocytes: inflicting, reflecting or resolving airway inflammation?

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Author

Summary, in English

The passage of infiltrated tissue granulocytes across airway epithelium into airway lumen is generally considered to be a pathogenic process in asthma and chronic obstructive pulmonary disease (COPD). An alternative hypothesis is proposed here-namely that the transepithelial egression of infiltrated leucocytes acts to rid diseased airway tissues of proinflammatory cells efficiently and non-injuriously. Several clinical observations previously discussed as 'unexpected' and 'puzzling' support this hypothesis. In acutely resolving allergen challenge-induced inflammation, in patients with mild asthma, airway wall eosinophils disappear without evidence of apoptosis but with evidence of a developing airway lumen eosinophilia. In the same postchallenge resolution phase, lymphocytes, neutrophils and mast cells exhibit peak numbers in airway lumen of individuals with asthma. In severe asthma requiring intubation, clinical improvement is similarly parallelled by a marked increase over several days in airway lumen neutrophils. Increased numbers of sputum neutrophils and lymphocytes also occur as symptoms improve in COPD over several months after smoking cessation. Conversely, when the transepithelial exit of leucocytes has been inhibited in inflamed animal airways the inflammation in the airway wall has been much aggravated. Finally, transepithelial egression of numerous granulocytes and lymphocytes clearly can occur without any harm to airway epithelial barriers. The present hypothesis of 'resolution through egression' provides a novel interpretation of common airway lumen data, cautions against administration of agents that impede leucocyte egression in inflammatory airway diseases and infers new approaches in disease resolution research.

Publishing year

2010

Language

English

Pages

1111-1115

Publication/Series

Thorax

Volume

65

Document type

Journal article

Publisher

BMJ Publishing Group

Topic

  • Respiratory Medicine and Allergy

Status

Published

Research group

  • Respiratory Immunopharmacology

ISBN/ISSN/Other

  • ISSN: 1468-3296