Phospholipase A2 functions in Pseudomonas aeruginosa-induced apoptosis.

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.