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

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

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  Google Scholar  Download references ACKNOWLEDGEMENTS We thank A. van Heeckeren for providing _P. aeruginosa_ strain M57-15. Supported by the Cystic Fibrosis Foundation (KARP01G0, NCRR M01

RR00069, and the Johns Hopkins and Cincinnati Children's Hospital Medical Center CF Research Development Program Centers). AUTHOR INFORMATION Author notes * Leah M Flick, Kiwon W Park

and Samir Softic: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Division of Molecular Immunology, Cincinnati Children's Hospital Medical Center, and

University of Cincinnati College of Medicine, Cincinnati, 45229, Ohio, USA Christopher L Karp, Leah M Flick, Samir Softic, Todd M Greer, Sowsan F Atabani & Yasmine Belkaid * Department

of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, 21287, Maryland, USA Kiwon W Park * Department of Chemistry, University of Southern California, Los Angeles,

90089, California, USA Raquel Keledjian, Rong Yang, Jasim Uddin & Nicos A Petasis * Department of Physiology, Johns Hopkins University, Baltimore, 21287, Maryland, USA William B Guggino

* Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, and University of Cincinnati College of Medicine, Cincinnati, 45229, Ohio, USA Yan Xu & Jeffrey A

Whitsett * Department of Pediatrics, University of Colorado Health Sciences Center, Mike McMorris Cystic Fibrosis Research and Treatment Center, the Children's Hospital, Denver, 80218,

Colorado, USA Frank J Accurso * Division of Immunobiology, Cincinnati Children's Hospital Medical Center, and University of Cincinnati College of Medicine, Cincinnati, 45229, Ohio, USA

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ARTICLE Karp, C., Flick, L., Park, K. _et al._ Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway. _Nat Immunol_ 5, 388–392 (2004).

https://doi.org/10.1038/ni1056 Download citation * Received: 15 December 2003 * Accepted: 28 January 2004 * Published: 21 March 2004 * Issue Date: 01 April 2004 * DOI:

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