Activation of Cytosolic Phospholipase A2α in Resident Peritoneal Macrophages by Listeria monocytogenes Involves Listeriolysin O and TLR2

• Published in: The Journal of biological chemistry Vol. 283; no. 8; p. 4744
• Main Authors: Shahid Noor, Howard Goldfine, Dawn E. Tucker, Saritha Suram, Laurel L. Lenz, Shizuo Akira, Satoshi Uematsu, Milena Girotti, Joseph V. Bonventre, Kevin Breuel, David L. Williams, Christina C. Leslie
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 22.02.2008
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M709956200

Eicosanoid production by macrophages is an early response to microbial infection that promotes acute inflammation. The intracellular pathogen Listeria monocytogenes stimulates arachidonic acid release and eicosanoid production from resident mouse peritoneal macrophages through activation of group IVA cytosolic phospholipase A 2 (cPLA 2 α). The ability of wild type L. monocytogenes (WTLM) to stimulate arachidonic acid release is partially dependent on the virulence factor listeriolysin O; however, WTLM and L. monocytogenes lacking listeriolysin O (Δ hly LM) induce similar levels of cyclooxygenase 2. Arachidonic acid release requires activation of MAPKs by WTLM and Δ hly LM. The attenuated release of arachidonic acid that is observed in TLR2 -/- and MyD88 -/- macrophages infected with WTLM and Δ hly LM correlates with diminished MAPK activation. WTLM but not Δ hly LM increases intracellular calcium, which is implicated in regulation of cPLA 2 α. Prostaglandin E 2 , prostaglandin I 2 , and leukotriene C 4 are produced by cPLA 2 α +/+ but not cPLA 2 α -/- macrophages in response to WTLM and Δ hly LM. Tumor necrosis factor (TNF)-α production is significantly lower in cPLA 2 α +/+ than in cPLA 2 α -/- macrophages infected with WTLM and Δ hly LM. Treatment of infected cPLA 2 α +/+ macrophages with the cyclooxygenase inhibitor indomethacin increases TNFα production to the level produced by cPLA 2 α -/- macrophages implicating prostaglandins in TNFα down-regulation. Therefore activation of cPLA 2 α in macrophages may impact immune responses to L. monocytogenes .