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 nonepithelial 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 interleukin 4 (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 threefold in the airway surface liquid of epithelia treated with IL-4. These results were confirmed at the functional level by measuring actin depolymerization using a fluorescence assay. Gelsolin protein was also upregulated in the airways of subjects with asthma. 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 patients with asthma. 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.
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 nonepithelial 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 interleukin 4 (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 threefold in the airway surface liquid of epithelia treated with IL-4. These results were confirmed at the functional level by measuring actin depolymerization using a fluorescence assay. Gelsolin protein was also upregulated in the airways of subjects with asthma. 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 patients with asthma. 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.
Authors: Ivana V Yang; Brent S Pedersen; Andrew H Liu; George T O'Connor; Dinesh Pillai; Meyer Kattan; Rana Tawil Misiak; Rebecca Gruchalla; Stanley J Szefler; Gurjit K Khurana Hershey; Carolyn Kercsmar; Adam Richards; Allen D Stevens; Christena A Kolakowski; Melanie Makhija; Christine A Sorkness; Rebecca Z Krouse; Cynthia Visness; Elizabeth J Davidson; Corinne E Hennessy; Richard J Martin; Alkis Togias; William W Busse; David A Schwartz Journal: J Allergy Clin Immunol Date: 2016-10-13 Impact factor: 10.793
Authors: John Audley; Emily F Gliniewicz; Kol A Zarember; Hanna S Hong; Gal Wald; Douglas B Kuhns; Elizabeth Kang; Harry L Malech; Anthony F Suffredini; Robert J Noveck; Mark J Dinubile; Susan L Levinson; Thomas P Stossel; John I Gallin Journal: Inflammation Date: 2020-09-04 Impact factor: 4.092
Authors: Christy L Ventura; Roger Higdon; Laura Hohmann; Daniel Martin; Eugene Kolker; H Denny Liggitt; Shawn J Skerrett; Craig E Rubens Journal: Infect Immun Date: 2008-10-13 Impact factor: 3.441