Role of Integrin alpha v beta 6 in Acute Lung Injury Induced by Pseudomonas aeruginosa

• Published in: Infection and immunity 2008-06, Vol.76 (6), p.2325-2332
• Main Authors: Song, Yuanlin, Pittet, Jean Francois, Huang, Xiaozhu, He, Hong, Lynch, Susan V, Violette, Shelia M, Weinreb, Paul H, Horan, Gerald S, Carmago, Amua, Sawa, Yoriko, Bernstein, Xin Liu, Wiener-Kronish, Jeanine P
• Format: Article
• Language: English
• Subjects: Pseudomonas aeruginosa
• ISSN: 0019-9567; 1098-5522

Deletion of integrin alpha v beta 6 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 beta 6 gene deletion would also protect against Pseudomonas aeruginosa-induced acute lung injury. Wild-type and littermate beta 6-null mice, as well as recombinant soluble TGF- beta receptor type II-Fc (rsTGF- beta RII-Fc) and anti- alpha v beta 6 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 beta 6 gene resulted in an overall increase in inflammatory cells in the lungs. Bacterial numbers from the lung homogenates of infected beta 6-null mice were significantly decreased compared to the numbers in the wild-type mice (1.6 x 10 super(6) CFU versus 4.2 x 10 super(6) CFU [P < 0.01]). There were no significant differences in P. aeruginosa-mediated increases in lung endothelial permeability between wild-type and beta 6-null mice. Similarly, pretreatment with the alpha v beta 6 antibody or with rsTGF- beta RII-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 alpha v beta 6 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.