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Science 6 July 2007:
Vol. 317. no. 5834, pp. 130 - 132
DOI: 10.1126/science.1142311

Reports

Host Resistance to Lung Infection Mediated by Major Vault Protein in Epithelial Cells

Michael P. Kowalski,1,2 Anne Dubouix-Bourandy,1,3 Milan Bajmoczi,1,4 David E. Golan,4,5 Tanweer Zaidi,1 Yamara S. Coutinho-Sledge,1 Melanie P. Gygi,6 Steven P. Gygi,6 Erik A. C. Wiemer,7 Gerald B. Pier1*

The airway epithelium plays an essential role in innate immunity to lung pathogens. Ribonucleoprotein particles primarily composed of major vault protein (MVP) are highly expressed in cells that encounter xenobiotics. However, a clear biologic function for MVP is not established. We report here that MVP is rapidly recruited to lipid rafts when human lung epithelial cells are infected with Pseudomonas aeruginosa, and maximal recruitment is dependent on bacterial binding to the cystic fibrosis transmembrane conductance regulator. MVP was also essential for optimal epithelial cell internalization and clearance of P. aeruginosa. These results suggest that MVP makes a substantial contribution to epithelial cell–mediated resistance to infection.

1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
2 Novartis Institute of Biomedical Research, Cambridge, MA 02139, USA.
3 Laboratoire de Bactériologie-Hygiène, Institut Fédératif de Biologie de Purpan, Toulouse, France.
4 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
5 Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
6 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
7 Department of Medical Oncology, Josephine Nefkens Institute, Erasmus Medical Center, 3015 GE Rotterdam, Netherlands.

* To whom correspondence should be addressed. E-mail: gpier{at}channing.harvard.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)