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However, it is still unknown which particular bacterial toxin and which cellular pathways are responsible for the increase in lung endothelial permeability induced by P. aeruginosa. Thus, the first objective of this study was to determine the mechanisms by which this species causes an increase in lung endothelial permeability. The results showed that ExoS and ExoT, two of the four known P. aeruginosa type III cytotoxins, were primarily responsible for bacterium-induced increases in protein permeability across the lung endothelium via an inhibition of Rac1 and an activation of the RhoA signaling pathway. In addition, inhibition of the \u03b1v\u03b25 integrin, a central regulator of lung vascular permeability, prevented these P. aeruginosa\u2013mediated increases in albumin flux due to endothelial permeability. Finally, prior activation of the stress protein response or adenoviral gene transfer of the inducible heat shock protein Hsp72 also inhibited the damaging effects of P. aeruginosa on the barrier function of lung endothelium. Taken together, these results demonstrate the critical role of the RhoA\/\u03b1v\u03b25 integrin pathway in mediating P. aeruginosa\u2013induced lung vascular permeability. In addition, activation of the stress protein response with pharmacologic inhibitors of Hsp90 may protect lungs against P. aeruginosa\u2013induced permeability changes.<\/jats:p>","DOI":"10.1165\/rcmb.2007-0454oc","type":"journal-article","created":{"date-parts":[[2008,8,14]],"date-time":"2008-08-14T21:49:29Z","timestamp":1218750569000},"page":"108-118","source":"Crossref","is-referenced-by-count":39,"title":["Role of Small GTPases and \u03b1v\u03b25 Integrin in\n                    <i>Pseudomonas aeruginosa<\/i>\n                    \u2013Induced Increase in Lung Endothelial Permeability"],"prefix":"10.1093","volume":"40","author":[{"given":"Michael T.","family":"Ganter","sequence":"first","affiliation":[{"name":"Departments of Anesthesia and Surgery, Laboratory of Surgical Research, and"},{"name":"Institute of Anesthesiology, University of Zurich, Zurich, 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