Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway

Christopher L. Karp, Leah M. Flick, Kiwon W. Park, Samir Softic, Todd M. Greer, Raquel Keledjian, Rong Yang, Jasmin Uddin, William B. Guggino, Sowsan F. Atabani, Yasmine Belkaid, Yan Xu, Jeffrey A. Whitsett, Frank J. Accurso, Marsha Wills-Karp, Nicos A. Petasis

Research output: Contribution to journalArticle

Abstract

In cystic fibrosis, dysregulated neutrophilic inflammation and chronic infection lead to progressive destruction of the airways. The underlying mechanisms have remained unclear. Lipoxins are anti-inflammatory lipid mediators that modulate neutrophilic inflammation. We report here that lipoxin concentrations in airway fluid were significantly suppressed in patients with cystic fibrosis compared to patients with other inflammatory lung conditions. We also show that administration of a metabolically stable lipoxin analog in a mouse model of the chronic airway inflammation and infection associated with cystic fibrosis suppressed neutrophilic inflammation, decreased pulmonary bacterial burden and attenuated disease severity. These findings suggest that there is a pathophysiologically important defect in lipoxin-mediated anti-inflammatory activity in the cystic fibrosis lung and that lipoxins have therapeutic potential in this lethal autosomal disease.

Original languageEnglish (US)
Pages (from-to)388-392
Number of pages5
JournalNature Immunology
Volume5
Issue number4
DOIs
StatePublished - Apr 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Karp, C. L., Flick, L. M., Park, K. W., Softic, S., Greer, T. M., Keledjian, R., Yang, R., Uddin, J., Guggino, W. B., Atabani, S. F., Belkaid, Y., Xu, Y., Whitsett, J. A., Accurso, F. J., Wills-Karp, M., & Petasis, N. A. (2004). Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway. Nature Immunology, 5(4), 388-392. https://doi.org/10.1038/ni1056