J Biol Chem 2005 Feb 15;280(6):4864-72. Epub 2004 Nov 15.
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine Duke University Medical Center, Durham, North Carolina 27710, USA
Pseudomonas aeruginosa is a major cause of pneumonia in patients with cystic fibrosis and other immuncompromising conditions. Here we showed that P. aeruginosa invades type I pneumocytes via a lipid raft-mediated mechanism. P. aeruginosa invasion of rat primary type I-like pneumocytes as well as a murine lung epithelial cell line 12 (MLE-12) is inhibited by drugs that remove membrane cholesterol and disrupt lipid rafts. Confocal microscopy demonstrated co-localization of intracellular P. aeruginosa with lipid raft components including caveolin-1 and -2. We generated caveolin-1 and -2 knockdowns in MLE-12 cells by using RNA interference techniques. Decreased expression of caveolin-2 significantly impaired the ability of P. aeruginosa to invade MLE-12 cells. In addition, the lipid raft-dependent tyrosine phosphorylation of caveolin-2 appeared to be a critical regulator of P. aeruginosa invasion.