This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.01431-07v1 76/6/2325    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Song, Y. Articles by Wiener-Kronish, J. P. PubMed PubMed Citation Articles by Song, Y. Articles by Wiener-Kronish, J. P.

 Previous Article  |  Next Article 

Infection and Immunity, June 2008, p. 2325-2332, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.01431-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Role of Integrin vβ6 in Acute Lung Injury Induced by Pseudomonas aeruginosa

Yuanlin Song,^1, Jean Francois Pittet,^1, Xiaozhu Huang,² Hong He,^1,4 Susan V. Lynch,¹ Shelia M. Violette,³ Paul H. Weinreb,³ Gerald S. Horan,³ Amua Carmago,¹ Yoriko Sawa,¹ Xin Liu Bernstein,² and Jeanine P. Wiener-Kronish^1*

Department of Anesthesia and Perioperative Care, University of California, San Francisco, California,¹ Department of Medicine, Lung Biology Center, University of California, San Francisco, California,² Biogen Idec, Inc., Cambridge, Massachusetts,³ Cancer Hospital, Fudan University, Shanghai 200032, People's Republic of China⁴

Received 24 October 2007/ Returned for modification 21 December 2007/ Accepted 13 March 2008

Deletion of integrin vβ6 has been associated with significant protection in experiments where lung injury was induced by bleomycin, lipophilic polysaccharides, and high tidal volume ventilation. This has led to the suggestion that antibody blockade of this integrin is a novel therapy for acute lung injury. We questioned whether β6 gene deletion would also protect against Pseudomonas aeruginosa-induced acute lung injury. Wild-type and littermate β6-null mice, as well as recombinant soluble TGF-β receptor type II-Fc (rsTGF-βRII-Fc) and anti-vβ6 treated wild-type mice, were instilled with live P. aeruginosa. Four or 8 h after bacterial instillation, the mice were euthanized, and either bronchoalveolar lavage fluid or lung homogenates were obtained. Deletion of the β6 gene resulted in an overall increase in inflammatory cells in the lungs. Bacterial numbers from the lung homogenates of infected β6-null mice were significantly decreased compared to the numbers in the wild-type mice (1.6 x 10⁶ CFU versus 4.2 x 10⁶ CFU [P < 0.01]). There were no significant differences in P. aeruginosa-mediated increases in lung endothelial permeability between wild-type and β6-null mice. Similarly, pretreatment with the vβ6 antibody or with rsTGF-βRII-Fc did not significantly affect the P. aeruginosa-induced lung injury or rate of survival compared to pretreatment with control immunoglobulin G. We conclude that deletion or inhibition of the integrin vβ6 did not protect animals from P. aeruginosa-induced lung injury. However, these therapies also did not increase the lung injury, suggesting that host defense was not compromised by this promising new therapy.

Published ahead of print on 31 March 2008.

Editor: J. B. Bliska

Y.S. and J.F.P. contributed equally to this study.