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Published ahead of print on August 11, 2005, doi:10.1164/rccm.200409-1185OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 9, November 2005, 1090-1096

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Submitted on September 9, 2004
Accepted on August 9, 2005

Gelsolin Secretion in Interleukin-4 Treated Bronchial Epithelia and in Asthmatic Airways

Giovanni Candiano1, Maurizio Bruschi1, Nicoletta Pedemonte2, Emanuela Caci2, Sabrina Liberatori3, Luca Bini3, Carlo Pellegrini4, Mario Vigano4, Brian J O'Connor5, Tak H Lee5, Luis J.V. Galietta2, and Olga Zegarra-Moran2*

1 Laboratory of Uremic Physiopathology, Istituto G. Gaslini, Genoa, Italy, 2 Laboratory of Molecular Genetics, Istituto G. Gaslini, Genoa, Italy, 3 Department of Molecular Biology, Laboratory of Functional Proteomics, Universita degli Studi di Siena, Siena, Italy, 4 Cardiosurgery Section, IRCCS Policlinico San Matteo, Universita degli Studi di Pavia, Pavia, Italy, 5 Department of Asthma, Allergy and Respiratory Science, King's College, GKT School of Medicine, London, United Kingdom

* To whom correspondence should be addressed. E-mail: ozegarra{at}unige.it.

Rationale: The airway surface liquid, the thin layer of liquid covering the airways, is essential for mucociliary clearance and as a barrier against microbial and other noxious agents. Proteins secreted into the airway surface liquid by epithelial and non-epithelial cells may be important in innate immunity and to improve the fluidity of mucous secretions. Objectives: We aimed to identify proteins specifically secreted into the airway surface liquid by human bronchial epithelial cells, in resting conditions and after treatment with IL-4, a cytokine released in asthma. Methods and Main Results: By using a proteomics approach we found that one of the most abundant proteins was gelsolin, which breaks down actin filaments. Gelsolin mRNA and protein secretion were increased three-fold in the airway surface liquid of epithelia treated with IL-4. These results were confirmed at the functional level by measuring actin depolymerisation using a fluorescence assay. Gelsolin protein was also upregulated in the airways of asthmatic subjects. Conclusions: Our findings indicate that gelsolin is released by epithelial cells into the airways and that its secretion is increased by IL-4 in vitro. In addition, we found that the concentration of both IL-4 and gelsolin were raised in the bronchoalveolar lavage of asthmatic patients. These results suggest that gelsolin might improve the fluidity of airway surface liquid in asthma by breaking down filamentous actin that may be released in large amounts by dying cells during inflammation.
Key words: epithelium, mucociliary clearance, actin




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