Phospholipase A 2 Functions in Pseudomonas aeruginosa - Induced Apoptosis

Abstract

ABSTRACT 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 A 2 (PLA 2 ), cultured epithelial cells, and fibroblasts, resulting in increased intracellular and extracellular arachidonic acid release. The use of different PLA 2 inhibitors revealed that P. aeruginosa -induced arachidonic acid release is mediated by activation of cytosolic PLA 2 (cPLA2), whereas iPLA 2 or sPLA 2 do not seem to be involved in the response to P. aeruginosa . Likewise, the cPLA 2 -specific inhibitors MAFP and AACOCF3 prevented apoptosis of cultured epithelial cells upon P. aeruginosa infection, whereas inhibitors specific for iPLA 2 or sPLA 2 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 cPLA 2 during P. aeruginosa infection plays an important role in the induction of host cell death.