Activation of cytosolic phospholipase A2alpha 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: Noor, Shahid, Goldfine, Howard, Tucker, Dawn E, Suram, Saritha, Lenz, Laurel L, Akira, Shizuo, Uematsu, Satoshi, Girotti, Milena, Bonventre, Joseph V, Breuel, Kevin, Williams, David L, Leslie, Christina C
• Format: Journal Article
• Language: English
• Published: United States 22.02.2008
• Subjects: Animals; Arachidonic Acids - genetics; Arachidonic Acids - immunology; Arachidonic Acids - metabolism; Bacterial Toxins - immunology; Bacterial Toxins - metabolism; Calcium - immunology; Calcium - metabolism; Calcium Signaling - drug effects; Calcium Signaling - physiology; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - immunology; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - pharmacology; Down-Regulation - drug effects; Down-Regulation - physiology; Enzyme Activation - drug effects; Enzyme Activation - physiology; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - immunology; Extracellular Signal-Regulated MAP Kinases - metabolism; Group IV Phospholipases A2 - genetics; Group IV Phospholipases A2 - immunology; Group IV Phospholipases A2 - metabolism; Heat-Shock Proteins - immunology; Heat-Shock Proteins - metabolism; Hemolysin Proteins - immunology; Hemolysin Proteins - metabolism; Indomethacin - pharmacology; Listeria monocytogenes - immunology; Listeriosis - enzymology; Listeriosis - genetics; Listeriosis - immunology; Macrophage Activation - drug effects; Macrophage Activation - physiology; Macrophages, Peritoneal - enzymology; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - microbiology; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Mice; Mice, Inbred ICR; Mice, Knockout; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - immunology; Myeloid Differentiation Factor 88 - metabolism; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 2 - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Virulence Factors - immunology; Virulence Factors - metabolism
• ISSN: 0021-9258

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 A2 (cPLA2alpha). 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 (DeltahlyLM) induce similar levels of cyclooxygenase 2. Arachidonic acid release requires activation of MAPKs by WTLM and DeltahlyLM. The attenuated release of arachidonic acid that is observed in TLR2-/- and MyD88-/- macrophages infected with WTLM and DeltahlyLM correlates with diminished MAPK activation. WTLM but not DeltahlyLM increases intracellular calcium, which is implicated in regulation of cPLA2alpha. Prostaglandin E2, prostaglandin I2, and leukotriene C4 are produced by cPLA2alpha+/+ but not cPLA2alpha-/- macrophages in response to WTLM and DeltahlyLM. Tumor necrosis factor (TNF)-alpha production is significantly lower in cPLA2alpha+/+ than in cPLA2alpha-/- macrophages infected with WTLM and DeltahlyLM. Treatment of infected cPLA2alpha+/+ macrophages with the cyclooxygenase inhibitor indomethacin increases TNFalpha production to the level produced by cPLA2alpha-/- macrophages implicating prostaglandins in TNFalpha down-regulation. Therefore activation of cPLA2alpha in macrophages may impact immune responses to L. monocytogenes.