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Phospholipase A₂ Functions in Pseudomonas aeruginosa- Induced Apoptosis

Department of Medical Microbiology, Technische Universitat Munich, 81675 Munich, Germany,¹ Department of Molecular Biology, University of Duisburg-Essen, 45122 Essen, Germany²

Received 21 December 2004/ Returned for modification 16 March 2005/ Accepted 19 October 2005

Pseudomonas aeruginosa, a gram-negative, facultative pathogen, causes severe and often even lethal infections in immunocompromised patients, as well as cystic fibrosis patients. We show here that a variety of P. aeruginosa strains activate phospholipase A₂ (PLA₂), cultured epithelial cells, and fibroblasts, resulting in increased intracellular and extracellular arachidonic acid release. The use of different PLA₂ inhibitors revealed that P. aeruginosa-induced arachidonic acid release is mediated by activation of cytosolic PLA₂ (cPLA2), whereas iPLA₂ or sPLA₂ do not seem to be involved in the response to P. aeruginosa. Likewise, the cPLA₂-specific inhibitors MAFP and AACOCF3 prevented apoptosis of cultured epithelial cells upon P. aeruginosa infection, whereas inhibitors specific for iPLA₂ or sPLA₂ were without effect. The physiological significance of these findings is indicated by an inhibition of apoptosis in tracheal epithelial cells upon in vivo infection with P. aeruginosa. The data indicate that arachidonic acid generation by activation of cPLA₂ during P. aeruginosa infection plays an important role in the induction of host cell death.

Editor: V. J. DiRita

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