Activation of cytosolic phospholipase A2alpha in resident peritoneal macrophages by Listeria monocytogenes involves listeriolysin O and TLR2.
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.
Noor
Shahid
S
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Goldfine
Howard
H
Tucker
Dawn E
DE
Suram
Saritha
S
Lenz
Laurel L
LL
Akira
Shizuo
S
Uematsu
Satoshi
S
Girotti
Milena
M
Bonventre
Joseph V
JV
Breuel
Kevin
K
Williams
David L
DL
Leslie
Christina C
CC
D000818:Animals; D001095:Arachidonic Acids / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000276:immunology / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism*
D001095:Arachidonic Acids; D001427:Bacterial Toxins; D016861:Cyclooxygenase Inhibitors; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D054513:Group IV Phospholipases A2; C038705:hlyA protein, Listeria monocytogenes; D002118:Calcium; D007213:Indomethacin