Chapter 19 : Lipid Mediators in Inflammation

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Lipid Mediators in Inflammation, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap19-1.gif /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap19-2.gif


Before we discuss lipids and their role in homeostasis and host defense, we will recount the essence of the inflammatory response. Inflammation is a reaction of the microcirculation; it’s a protective response initiated after infection or injury. While both local and systemic responses can be activated, inflammation is an essential biological process with the objective of eliminating the inciting stimulus, promoting tissue repair/wound healing, and, in the case of infection, establishing memory such that the host mounts a faster and more specific response upon a future encounter. The acute inflammatory response is a complex yet highly coordinated sequence of events involving a large number of molecular, cellular, and physiological changes. It begins with the production of soluble mediators (complement, chemokines, cytokines, eicosanoids—including prostaglandins [PGs], free radicals, vasoactive amines, etc.) by resident cells in the injured/infected tissue (i.e., tissue macrophages, dendritic cells, lymphocytes, endothelial cells, fibroblasts, and mast cells), concomitant with the upregulation of cell adhesion molecules on both leukocytes and endothelial cells that promote the exudation of proteins and influx of granulocytes from blood ( ). Upon arrival, these leukocytes, typically polymorphonuclear leukocytes (PMNs) in the case of nonspecific inflammation or eosinophils in response to allergens, function primarily to phagocytose and eliminate foreign microorganisms via distinct intracellular (superoxide, myeloperoxidase, proteases, and lactoferrins) and/or extracellular (neutrophil extracellular traps) killing mechanisms ( ). It is likely that the magnitude of the infectious load and its eventual neutralization signal the next phase of active anti-inflammation and proresolution ( ).

Citation: Bennett M, Gilroy D. 2017. Lipid Mediators in Inflammation, p 343-366. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0035-2016
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Serhan C,, Ward P,, Gilroy D . 2010. Fundamentals of Inflammation. Cambridge University Press, Cambridge, United Kingdom.
2. Segal AW . 2005. How neutrophils kill microbes. Annu Rev Immunol 23 : 197223.
3. Serhan CN,, Savill J . 2005. Resolution of inflammation: the beginning programs the end. Nat Immunol 6 : 11911197.
4. Majno G,, Joris I . 2004. Cells, Tissues and Disease: Principles of General Pathology, 2nd ed. Oxford University Press, New York, NY.
5. Buckley CD,, Gilroy DW,, Serhan CN . 2014. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 40 : 315327.
6. Buckley CD,, Gilroy DW,, Serhan CN,, Stockinger B,, Tak PP . 2013. The resolution of inflammation. Nat Rev Immunol 13 : 5966.
7. Segal AW,, Geisow M,, Garcia R,, Harper A,, Miller R . 1981. The respiratory burst of phagocytic cells is associated with a rise in vacuolar pH. Nature 290 : 406409.
8. Gilroy DW,, Colville-Nash PR,, McMaster S,, Sawatzky DA,, Willoughby DA,, Lawrence T . 2003. Inducible cyclooxygenase-derived 15deoxyΔ12–14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and macrophage apoptosis. FASEB J 17 : 22692271.
9. Nibbs RJ,, Graham GJ . 2013. Immune regulation by atypical chemokine receptors. Nat Rev Immunol 13 : 815829.
10. Ariel A,, Fredman G,, Sun YP,, Kantarci A,, Van Dyke TE,, Luster AD,, Serhan CN . 2006. Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nat Immunol 7 : 12091216.
11. Piper P,, Vane J . 1971. The release of prostaglandins from lung and other tissues. Ann N Y Acad Sci 180 : 363385.
12. Samuelsson B,, Dahlén SE,, Lindgren JA,, Rouzer CA,, Serhan CN . 1987. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237 : 11711176.
13. Serhan CN,, Hamberg M,, Samuelsson B . 1984. Trihydroxytetraenes: a novel series of compounds formed from arachidonic acid in human leukocytes. Biochem Biophys Res Commun 118 : 943949.
14. Capdevila JH,, Falck JR,, Dishman E,, Karara A . 1990. Cytochrome P-450 arachidonate oxygenase. Methods Enzymol 187 : 385394.
15. Pagels WR,, Sachs RJ,, Marnett LJ,, Dewitt DL,, Day JS,, Smith WL . 1983. Immunochemical evidence for the involvement of prostaglandin H synthase in hydroperoxide-dependent oxidations by ram seminal vesicle microsomes. J Biol Chem 258 : 65176523.
16. Hamberg M,, Samuelsson B . 1973. Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis. Proc Natl Acad Sci U S A 70 : 899903.
17. Nugteren DH,, Hazelhof E . 1973. Isolation and properties of intermediates in prostaglandin biosynthesis. Biochim Biophys Acta 326 : 448461.
18. Dubois RN,, Abramson SB,, Crofford L,, Gupta RA,, Simon LS,, Van De Putte LB,, Lipsky PE . 1998. Cyclooxygenase in biology and disease. FASEB J 12 : 10631073.
19. Shimizu T,, Yamamoto S,, Hayaishi O . 1982. Purification of PGH-PGD isomerase from rat brain. Methods Enzymol 86 : 7377.
20. Tanaka Y,, Ward SL,, Smith WL . 1987. Immunochemical and kinetic evidence for two different prostaglandin H-prostaglandin E isomerases in sheep vesicular gland microsomes. J Biol Chem 262 : 13741381.
21. Hayashi H,, Fujii Y,, Watanabe K,, Urade Y,, Hayaishi O . 1989. Enzymatic conversion of prostaglandin H2 to prostaglandin F by aldehyde reductase from human liver: comparison to the prostaglandin F synthetase from bovine lung. J Biol Chem 264 : 10361040.
22. DeWitt DL,, Smith WL . 1983. Purification of prostacyclin synthase from bovine aorta by immunoaffinity chromatography. Evidence that the enzyme is a hemoprotein. J Biol Chem 258 : 32853293.
23. Ullrich V,, Haurand M . 1983. Thromboxane synthase as a cytochrome P450 enzyme. Adv Prostaglandin Thromboxane Leukot Res 11 : 105110.
24. Bezugla Y,, Kolada A,, Kamionka S,, Bernard B,, Scheibe R,, Dieter P . 2006. COX-1 and COX-2 contribute differentially to the LPS-induced release of PGE2 and TxA2 in liver macrophages. Prostaglandins Other Lipid Mediat 79 : 93100.
25. Naraba H,, Murakami M,, Matsumoto H,, Shimbara S,, Ueno A,, Kudo I,, Oh-ishi S . 1998. Segregated coupling of phospholipases A2, cyclooxygenases, and terminal prostanoid synthases in different phases of prostanoid biosynthesis in rat peritoneal macrophages. J Immunol 160 : 29742982.
26. Jakobsson PJ,, Thorén S,, Morgenstern R,, Samuelsson B . 1999. Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A 96 : 72207225.
27. Penglis PS,, Cleland LG,, Demasi M,, Caughey GE,, James MJ . 2000. Differential regulation of prostaglandin E2 and thromboxane A2 production in human monocytes: implications for the use of cyclooxygenase inhibitors. J Immunol 165 : 16051611.
28. Brock TG,, McNish RW,, Peters-Golden M . 1999. Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E2 . J Biol Chem 274 : 1166011666.
29. Hirai H,, Tanaka K,, Yoshie O,, Ogawa K,, Kenmotsu K,, Takamori Y,, Ichimasa M,, Sugamura K,, Nakamura M,, Takano S,, Nagata K . 2001. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med 193 : 255261.
30. Monneret G,, Gravel S,, Diamond M,, Rokach J,, Powell WS . 2001. Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor. Blood 98 : 19421948.
31. Xue L,, Gyles SL,, Wettey FR,, Gazi L,, Townsend E,, Hunter MG,, Pettipher R . 2005. Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J Immunol 175 : 65316536.
32. von Euler US . 1936. On the specific vaso-dilating and plain muscle stimulating substances from accessory genital glands in man and certain animals (prostaglandin and vesiglandin). J Physiol 88 : 213234.
33. Eckenfels A,, Vane JR . 1972. Prostaglandins, oxygen tension and smooth muscle tone. Br J Pharmacol 45 : 451462.
34. Ferreira SH,, Herman A,, Vane JR . 1972. Proceedings: prostaglandin generation maintains the smooth muscle tone of the rabbit isolated jejunum. Br J Pharmacol 44 : 328P329P.
35. Main IH . 1964. The inhibitory actions of prostaglandins on respiratory smooth muscle. Br Pharmacol Chemother 22 : 511519.
36. Williams TJ . 1979. Prostaglandin E2, prostaglandin I2 and the vascular changes of inflammation. Br J Pharmacol 65 : 517524.
37. Williams TJ,, Jose PJ . 1981. Mediation of increased vascular permeability after complement activation. Histamine-independent action of rabbit C5a. J Exp Med 153 : 136153.
38. Ferreira SH,, Nakamura M,, de Abreu Castro MS . 1978. The hyperalgesic effects of prostacyclin and prostaglandin E2 . Prostaglandins 16 : 3137.
39. Feldberg W,, Gupta KP . 1973. Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid. J Physiol 228 : 4153.
40. Feldberg W,, Saxena PN . 1971. Fever produced by prostaglandin E1 . J Physiol 217 : 547556.
41. Milton AS,, Wendlandt S . 1971. Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. J Physiol 218 : 325336.
42. Moncada S,, Gryglewski R,, Bunting S,, Vane JR . 1976. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263 : 663665.
43. Kaley G,, Hintze TH,, Panzenbeck M,, Messina EJ . 1985. Role of prostaglandins in microcirculatory function. Adv Prostaglandin Thromboxane Leukot Res 13 : 2735.
44. Hata AN,, Breyer RM . 2004. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther 103 : 147166.
45. Higgs EA,, Moncada S,, Vane JR . 1978. Inflammatory effects of prostacyclin (PGI2) and 6-oxo-PGF in the rat paw. Prostaglandins 16 : 153162.
46. Komoriya K,, Ohmori H,, Azuma A,, Kurozumi S,, Hashimoto Y,, Nicolaou KC,, Barnette WE,, Magolda RL . 1978. Prostaglandin I2 as a potentiator of acute inflammation in rats. Prostaglandins 15 : 557564.
47. Lewis AJ,, Nelson DJ,, Sugrue MF . 1975. On the ability of prostaglandin E1, and arachidonic acid to modulate experimentally induced oedema in the rat paw. Br J Pharmacol 55 : 5156.
48. Moncada S,, Ferreira SH,, Vane JR . 1973. Prostaglandins, aspirin-like drugs and the oedema of inflammation. Nature 246 : 217219.
49. Williams TJ,, Morley J . 1973. Prostaglandins as potentiators of increased vascular permeability in inflammation. Nature 246 : 215217.
50. Yuhki K,, Ueno A,, Naraba H,, Kojima F,, Ushikubi F,, Narumiya S,, Oh-ishi S . 2004. Prostaglandin receptors EP2, EP3, and IP mediate exudate formation in carrageenin-induced mouse pleurisy. J Pharmacol Exp Ther 311 : 12181224.
51. Yuhki K,, Ushikubi F,, Naraba H,, Ueno A,, Kato H,, Kojima F,, Narumiya S,, Sugimoto Y,, Matsushita M,, Oh-Ishi S . 2008. Prostaglandin I2 plays a key role in zymosan-induced mouse pleurisy. J Pharmacol Exp Ther 325 : 601609.
52. Saxena PN,, Beg MM,, Singhal KC,, Ahmad M . 1979. Prostaglandin-like activity in the cerebrospinal fluid of febrile patients. Indian J Med Res 70 : 495498.
53. Dantzer R,, Konsman JP,, Bluthé RM,, Kelley KW . 2000. Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent? Auton Neurosci 85 : 6065.
54. Ek M,, Kurosawa M,, Lundeberg T,, Ericsson A . 1998. Activation of vagal afferents after intravenous injection of interleukin-1beta: role of endogenous prostaglandins. J Neurosci 18 : 94719479.
55. Lazarus M,, Yoshida K,, Coppari R,, Bass CE,, Mochizuki T,, Lowell BB,, Saper CB . 2007. EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responses. Nat Neurosci 10 : 11311133.
56. Ushikubi F,, Segi E,, Sugimoto Y,, Murata T,, Matsuoka T,, Kobayashi T,, Hizaki H,, Tuboi K,, Katsuyama M,, Ichikawa A,, Tanaka T,, Yoshida N,, Narumiya S . 1998. Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3 . Nature 395 : 281284.
57. Madden CJ,, Morrison SF . 2003. Excitatory amino acid receptor activation in the raphe pallidus area mediates prostaglandin-evoked thermogenesis. Neuroscience 122 : 515.
58. Madden CJ,, Morrison SF . 2004. Excitatory amino acid receptors in the dorsomedial hypothalamus mediate prostaglandin-evoked thermogenesis in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 286 : R320R325.
59. Morrison SF . 2001. Differential regulation of sympathetic outflows to vasoconstrictor and thermoregulatory effectors. Ann N Y Acad Sci 940 : 286298.
60. Morrison SF . 2003. Raphe pallidus neurons mediate prostaglandin E2-evoked increases in brown adipose tissue thermogenesis. Neuroscience 121 : 1724.
61. Morrison SF . 2004. Central pathways controlling brown adipose tissue thermogenesis. News Physiol Sci 19 : 6774.
62. Ahmadi S,, Lippross S,, Neuhuber WL,, Zeilhofer HU . 2002. PGE2 selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons. Nat Neurosci 5 : 3440.
63. Juhlin L,, Michaëlsson G . 1969. Cutaneous vascular reactions to prostaglandins in healthy subjects and in patients with urticaria and atopic dermatitis. Acta Derm Venereol 49 : 251261.
64. Lin CR,, Amaya F,, Barrett L,, Wang H,, Takada J,, Samad TA,, Woolf CJ . 2006. Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity. J Pharmacol Exp Ther 319 : 10961103.
65. McAdam BF,, Mardini IA,, Habib A,, Burke A,, Lawson JA,, Kapoor S,, FitzGerald GA . 2000. Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation. J Clin Invest 105 : 14731482.
66. Moriyama T,, Higashi T,, Togashi K,, Iida T,, Segi E,, Sugimoto Y,, Tominaga T,, Narumiya S,, Tominaga M . 2005. Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins. Mol Pain 1 : 3. doi:10.1186/1744-8069-1-3.
67. Murata T,, Ushikubi F,, Matsuoka T,, Hirata M,, Yamasaki A,, Sugimoto Y,, Ichikawa A,, Aze Y,, Tanaka T,, Yoshida N,, Ueno A,, Oh-ishi S,, Narumiya S . 1997. Altered pain perception and inflammatory response in mice lacking prostacyclin receptor. Nature 388 : 678682.
68. Reinold H,, Ahmadi S,, Depner UB,, Layh B,, Heindl C,, Hamza M,, Pahl A,, Brune K,, Narumiya S,, Müller U,, Zeilhofer HU . 2005. Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype. J Clin Invest 115 : 673679.
69. Solomon LM,, Juhlin L,, Kirschenbaum MB . 1968. Prostaglandin on cutaneous vasculature. J Invest Dermatol 51 : 280282.
70. Ueno A,, Matsumoto H,, Naraba H,, Ikeda Y,, Ushikubi F,, Matsuoka T,, Narumiya S,, Sugimoto Y,, Ichikawa A,, Oh-ishi S . 2001. Major roles of prostanoid receptors IP and EP3 in endotoxin-induced enhancement of pain perception. Biochem Pharmacol 62 : 157160.
71. Smyth EM,, Grosser T,, Wang M,, Yu Y,, FitzGerald GA . 2009. Prostanoids in health and disease. J Lipid Res 50(Suppl): S423S428.
72. García Rodríguez LA,, Tacconelli S,, Patrignani P . 2008. Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol 52 : 16281636.
73. Grosser T,, Fries S,, FitzGerald GA . 2006. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest 116 : 415.
74. Xiao CY,, Hara A,, Yuhki K,, Fujino T,, Ma H,, Okada Y,, Takahata O,, Yamada T,, Murata T,, Narumiya S,, Ushikubi F . 2001. Roles of prostaglandin I2 and thromboxane A2 in cardiac ischemia-reperfusion injury: a study using mice lacking their respective receptors. Circulation 104 : 22102215.
75. Degousee N,, Fazel S,, Angoulvant D,, Stefanski E,, Pawelzik SC,, Korotkova M,, Arab S,, Liu P,, Lindsay TF,, Zhuo S,, Butany J,, Li RK,, Audoly L,, Schmidt R,, Angioni C,, Geisslinger G,, Jakobsson PJ,, Rubin BB . 2008. Microsomal prostaglandin E2 synthase-1 deletion leads to adverse left ventricular remodeling after myocardial infarction. Circulation 117 : 17011710.
76. Qian JY,, Harding P,, Liu Y,, Shesely E,, Yang XP,, LaPointe MC . 2008. Reduced cardiac remodeling and function in cardiac-specific EP4 receptor knockout mice with myocardial infarction. Hypertension 51 : 560566.
77. Bunting S,, Moncada S,, Vane JR . 1983. The prostacyclin-thromboxane A2 balance: pathophysiological and therapeutic implications. Br Med Bull 39 : 271276.
78. FitzGerald GA . 2003. COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Drug Discov 2 : 879890.
79. de Nucci G,, Gryglewski RJ,, Warner TD,, Vane JR . 1988. Receptor-mediated release of endothelium-derived relaxing factor and prostacyclin from bovine aortic endothelial cells is coupled. Proc Natl Acad Sci U S A 85 : 23342338.
80. Palmer RM,, Ferrige AG,, Moncada S . 1987. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327 : 524526.
81. Ellis EF,, Oelz O,, Roberts LJ II,, Payne NA,, Sweetman BJ,, Nies AS,, Oates JA . 1976. Coronary arterial smooth muscle contraction by a substance released from platelets: evidence that it is thromboxane A2 . Science 193 : 11351137.
82. Hamberg M,, Svensson J,, Samuelsson B . 1975. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A 72 : 29942998.
83. Salzman PM,, Salmon JA,, Moncada S . 1980. Prostacyclin and thromboxane A2 synthesis by rabbit pulmonary artery. J Pharmacol Exp Ther 215 : 240247.
84. Rocca B,, Secchiero P,, Ciabattoni G,, Ranelletti FO,, Catani L,, Guidotti L,, Melloni E,, Maggiano N,, Zauli G,, Patrono C . 2002. Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets. Proc Natl Acad Sci U S A 99 : 76347639.
85. Aronoff DM,, Carstens JK,, Chen GH,, Toews GB,, Peters-Golden M . 2006. Short communication: differences between macrophages and dendritic cells in the cyclic AMP-dependent regulation of lipopolysaccharide-induced cytokine and chemokine synthesis. J Interferon Cytokine Res 26 : 827833.
86. Luo M,, Jones SM,, Phare SM,, Coffey MJ,, Peters-Golden M,, Brock TG . 2004. Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5-lipoxygenase on serine 523. J Biol Chem 279 : 4151241520.
87. van der Pouw Kraan TC,, van Lier RA,, Aarden LA . 1995. PGE2 and the immune response. A central role for prostaglandin E2 in downregulating the inflammatory immune response. Mol Med Today 1 : 61.
88. Aronoff DM,, Canetti C,, Peters-Golden M . 2004. Prostaglandin E2 inhibits alveolar macrophage phagocytosis through an E-prostanoid 2 receptor-mediated increase in intracellular cyclic AMP. J Immunol 173 : 559565.
89. Rossi AG,, McCutcheon JC,, Roy N,, Chilvers ER,, Haslett C,, Dransfield I . 1998. Regulation of macrophage phagocytosis of apoptotic cells by cAMP. J Immunol 160 : 35623568.
90. Serezani CH,, Chung J,, Ballinger MN,, Moore BB,, Aronoff DM,, Peters-Golden M . 2007. Prostaglandin E2 suppresses bacterial killing in alveolar macrophages by inhibiting NADPH oxidase. Am J Respir Cell Mol Biol 37 : 562570.
91. Soares AC,, Souza DG,, Pinho V,, Vieira AT,, Barsante MM,, Nicoli JR,, Teixeira M . 2003. Impaired host defense to Klebsiella pneumoniae infection in mice treated with the PDE4 inhibitor rolipram. Br J Pharmacol 140 : 855862.
92. Weinberg DA,, Weston LK,, Kaplan JE . 1985. Influence of prostaglandin I2 on fibronectin-mediated phagocytosis in vivo and in vitro. J Leukoc Biol 37 : 151159.
93. Ydrenius L,, Majeed M,, Rasmusson BJ,, Stendahl O,, Särndahl E . 2000. Activation of cAMP-dependent protein kinase is necessary for actin rearrangements in human neutrophils during phagocytosis. J Leukoc Biol 67 : 520528.
94. Aronoff DM,, Peres CM,, Serezani CH,, Ballinger MN,, Carstens JK,, Coleman N,, Moore BB,, Peebles RS,, Faccioli LH,, Peters-Golden M . 2007. Synthetic prostacyclin analogs differentially regulate macrophage function via distinct analog-receptor binding specificities. J Immunol 178 : 16281634.
95. Brandwein SR . 1986. Regulation of interleukin 1 production by mouse peritoneal macrophages. Effects of arachidonic acid metabolites, cyclic nucleotides, and interferons. J Biol Chem 261 : 86248632.
96. Kunkel SL,, Spengler M,, May MA,, Spengler R,, Larrick J,, Remick D . 1988. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem 263 : 53805384.
97. Kunkel SL,, Wiggins RC,, Chensue SW,, Larrick J . 1986. Regulation of macrophage tumor necrosis factor production by prostaglandin E2 . Biochem Biophys Res Commun 137 : 404410.
98. Takayama K,, García-Cardena G,, Sukhova GK,, Comander J,, Gimbrone MA Jr,, Libby P . 2002. Prostaglandin E2 suppresses chemokine production in human macrophages through the EP4 receptor. J Biol Chem 277 : 4414744154.
99. van der Pouw Kraan TC,, Boeije LC,, Snijders A,, Smeenk RJ,, Wijdenes J,, Aarden LA . 1996. Regulation of IL-12 production by human monocytes and the influence of prostaglandin E2 . Ann N Y Acad Sci 795 : 147157.
100. Xu XJ,, Reichner JS,, Mastrofrancesco B,, Henry WL Jr,, Albina JE . 2008. Prostaglandin E2 suppresses lipopolysaccharide-stimulated IFN-β production. J Immunol 180 : 21252131.
101. Harizi H,, Juzan M,, Pitard V,, Moreau JF,, Gualde N . 2002. Cyclooxygenase-2-issued prostaglandin E2 enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. J Immunol 168 : 22552263.
102. Hinson RM,, Williams JA,, Shacter E . 1996. Elevated interleukin 6 is induced by prostaglandin E2 in a murine model of inflammation: possible role of cyclooxygenase-2. Proc Natl Acad Sci U S A 93 : 48854890.
103. Starczewski M,, Voigtmann R,, Peskar BA,, Peskar BM . 1984. Plasma levels of 15-keto-13,14-dihydro-prostaglandin E2 in patients with bronchogenic carcinoma. Prostaglandins Leukot Med 13 : 249258.
104. Hayek MG,, Mura C,, Wu D,, Beharka AA,, Han SN,, Paulson KE,, Hwang D,, Meydani SN . 1997. Enhanced expression of inducible cyclooxygenase with age in murine macrophages. J Immunol 159 : 24452451.
105. Medjane S,, Raymond B,, Wu Y,, Touqui L . 2005. Impact of CFTR ΔF508 mutation on prostaglandin E2 production and type IIA phospholipase A2 expression by pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 289 : L816L824.
106. Strandvik B,, Svensson E,, Seyberth HW . 1996. Prostanoid biosynthesis in patients with cystic fibrosis. Prostaglandins Leukot Essent Fatty Acids 55 : 419425.
107. Levy BD,, Clish CB,, Schmidt B,, Gronert K,, Serhan CN . 2001. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2 : 612619.
108. Hong S,, Gronert K,, Devchand PR,, Moussignac RL,, Serhan CN . 2003. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 278 : 1467714687.
109. Marcheselli VL,, Hong S,, Lukiw WJ,, Tian XH,, Gronert K,, Musto A,, Hardy M,, Gimenez JM,, Chiang N,, Serhan CN,, Bazan NG . 2003. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 278 : 4380743817.
110. Serhan CN,, Clish CB,, Brannon J,, Colgan SP,, Chiang N,, Gronert K . 2000. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 192 : 11971204.
111. Serhan CN,, Hong S,, Gronert K,, Colgan SP,, Devchand PR,, Mirick G,, Moussignac RL . 2002. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 196 : 10251037.
112. Clark RB,, Bishop-Bailey D,, Estrada-Hernandez T,, Hla T,, Puddington L,, Padula SJ . 2000. The nuclear receptor PPARγ and immunoregulation: PPARγ mediates inhibition of helper T cell responses. J Immunol 164 : 13641371.
113. Combs CK,, Johnson DE,, Karlo JC,, Cannady SB,, Landreth GE . 2000. Inflammatory mechanisms in Alzheimer’s disease: inhibition of β-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARγ agonists. J Neurosci 20 : 558567.
114. Diab A,, Deng C,, Smith JD,, Hussain RZ,, Phanavanh B,, Lovett-Racke AE,, Drew PD,, Racke MK . 2002. Peroxisome proliferator-activated receptor-γ agonist 15-deoxy-Δ12,14-prostaglandin J2 ameliorates experimental autoimmune encephalomyelitis. J Immunol 168 : 25082515.
115. Kawahito Y,, Kondo M,, Tsubouchi Y,, Hashiramoto A,, Bishop-Bailey D,, Inoue K,, Kohno M,, Yamada R,, Hla T,, Sano H . 2000. 15-Deoxy-Δ12,14-PGJ2 induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats. J Clin Invest 106 : 189197.
116. Reilly CM,, Oates JC,, Cook JA,, Morrow JD,, Halushka PV,, Gilkeson GS . 2000. Inhibition of mesangial cell nitric oxide in MRL/lpr mice by prostaglandin J2 and proliferator activation receptor-γ agonists. J Immunol 164 : 14981504.
117. Kim EH,, Na HK,, Surh YJ . 2006. Upregulation of VEGF by 15-deoxy-Δ12,14-prostaglandin J2 via heme oxygenase-1 and ERK1/2 signaling in MCF-7 cells. Ann N Y Acad Sci 1090 : 375384.
118. Oliva JL,, Pérez-Sala D,, Castrillo A,, Martínez N,, Cañada FJ,, Boscá L,, Rojas JM . 2003. The cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 binds to and activates H-Ras. Proc Natl Acad Sci USA 100 : 47724777.
119. Renedo M,, Gayarre J,, García-Domínguez CA,, Pérez-Rodríguez A,, Prieto A,, Cañada FJ,, Rojas JM,, Pérez-Sala D . 2007. Modification and activation of Ras proteins by electrophilic prostanoids with different structure are site-selective. Biochemistry 46 : 66076616.
120. Khan MM . 1995. Regulation of IL-4 and IL-5 secretion by histamine and PGE2 . Adv Exp Med Biol 383 : 3542.
121. Jiang C,, Ting AT,, Seed B . 1998. PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 391 : 8286.
122. Ricote M,, Li AC,, Willson TM,, Kelly CJ,, Glass CK . 1998. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 391 : 7982.
123. Cernuda-Morollón E,, Pineda-Molina E,, Cañada FJ,, Pérez-Sala D . 2001. 15-Deoxy-Δ12,14-prostaglandin J2 inhibition of NF-κB-DNA binding through covalent modification of the p50 subunit. J Biol Chem 276 : 3553035536.
124. Rossi A,, Kapahi P,, Natoli G,, Takahashi T,, Chen Y,, Karin M,, Santoro MG . 2000. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 403 : 103108.
125. Straus DS,, Pascual G,, Li M,, Welch JS,, Ricote M,, Hsiang CH,, Sengchanthalangsy LL,, Ghosh G,, Glass CK . 2000. 15-Deoxy-Δ12,14-prostaglandin J2 inhibits multiple steps in the NF-κB signaling pathway. Proc Natl Acad Sci U S A 97 : 48444849.
126. Jackson SM,, Parhami F,, Xi XP,, Berliner JA,, Hsueh WA,, Law RE,, Demer LL . 1999. Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. Arterioscler Thromb Vasc Biol 19 : 20942104.
127. Pasceri V,, Wu HD,, Willerson JT,, Yeh ET . 2000. Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-γ activators. Circulation 101 : 235238.
128. Zhang X,, Wang JM,, Gong WH,, Mukaida N,, Young HA . 2001. Differential regulation of chemokine gene expression by 15-deoxy-Δ12,14 prostaglandin J2 . J Immunol 166 : 71047111.
129. Lawrence T . 2002. Modulation of inflammation in vivo through induction of the heat shock response, effects on NF-κB activation. Inflamm Res 51 : 108109.
130. Bishop-Bailey D,, Hla T . 1999. Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Δ12,14-prostaglandin J2 . J Biol Chem 274 : 1704217048.
131. Khoshnan A,, Tindell C,, Laux I,, Bae D,, Bennett B,, Nel AE . 2000. The NF-κB cascade is important in Bcl-xL expression and for the anti-apoptotic effects of the CD28 receptor in primary human CD4+ lymphocytes. J Immunol 165 : 17431754.
132. Lawrence T,, Gilroy DW,, Colville-Nash PR,, Willoughby DA . 2001. Possible new role for NF-κB in the resolution of inflammation. Nat Med 7 : 12911297.
133. Ward C,, Dransfield I,, Murray J,, Farrow SN,, Haslett C,, Rossi AG . 2002. Prostaglandin D2 and its metabolites induce caspase-dependent granulocyte apoptosis that is mediated via inhibition of IκBα degradation using a peroxisome proliferator-activated receptor-γ-independent mechanism. J Immunol 168 : 62326243.
134. Trivedi SG,, Newson J,, Rajakariar R,, Jacques TS,, Hannon R,, Kanaoka Y,, Eguchi N,, Colville-Nash P,, Gilroy DW . 2006. Essential role for hematopoietic prostaglandin D2 synthase in the control of delayed type hypersensitivity. Proc Natl Acad Sci U S A 103 : 51795184.
135. Lewis RA,, Austen KF,, Drazen JM,, Clark DA,, Marfat A,, Corey EJ . 1980. Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci U S A 77 : 37103714.
136. Borgeat P,, Samuelsson B . 1979. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A 76 : 21482152.
137. Smith MJ . 1979. Prostaglandins and the polymorphonuclear leucocyte. Agents Actions Suppl 1979(6): 91103.
138. Funk CD . 2001. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294 : 18711875.
139. Minami M,, Ohno S,, Kawasaki H,, Rådmark O,, Samuelsson B,, Jörnvall H,, Shimizu T,, Seyama Y,, Suzuki K . 1987. Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis. J Biol Chem 262 : 1387313876.
140. Hammarström S,, Orning L,, Bernström K . 1985. Metabolism of leukotrienes. Mol Cell Biochem 69 : 716.
141. Lam BK,, Gagnon L,, Austen KF,, Soberman RJ . 1990. The mechanism of leukotriene B4 export from human polymorphonuclear leukocytes. J Biol Chem 265 : 1343813441.
142. Leier I,, Jedlitschky G,, Buchholz U,, Keppler D . 1994. Characterization of the ATP-dependent leukotriene C4 export carrier in mastocytoma cells. Eur J Biochem 220 : 599606.
143. Rouzer CA,, Samuelsson B . 1985. On the nature of the 5-lipoxygenase reaction in human leukocytes: enzyme purification and requirement for multiple stimulatory factors. Proc Natl Acad Sci U S A 82 : 60406044.
144. Ochi K,, Yoshimoto T,, Yamamoto S,, Taniguchi K,, Miyamoto T . 1983. Arachidonate 5-lipoxygenase of guinea pig peritoneal polymorphonuclear leukocytes. Activation by adenosine 5′-triphosphate. J Biol Chem 258 : 57545758.
145. Werz O,, Szellas D,, Steinhilber D,, Rådmark O . 2002. Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). J Biol Chem 277 : 1479314800.
146. Kanaoka Y,, Boyce JA . 2004. Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses. J Immunol 173 : 15031510.
147. Tager AM,, Luster AD . 2003. BLT1 and BLT2: the leukotriene B4 receptors. Prostaglandins Leukot Essent Fatty Acids 69 : 123134.
148. Lynch KR,, O’Neill GP,, Liu Q,, Im DS,, Sawyer N,, Metters KM,, Coulombe N,, Abramovitz M,, Figueroa DJ,, Zeng Z,, Connolly BM,, Bai C,, Austin CP,, Chateauneuf A,, Stocco R,, Greig GM,, Kargman S,, Hooks SB,, Hosfield E,, Williams DL Jr,, Ford-Hutchinson AW,, Caskey CT,, Evans JF . 1999. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature 399 : 789793.
149. Beller TC,, Friend DS,, Maekawa A,, Lam BK,, Austen KF,, Kanaoka Y . 2004. Cysteinyl leukotriene 1 receptor controls the severity of chronic pulmonary inflammation and fibrosis. Proc Natl Acad Sci U S A 101 : 30473052.
150. Hui Y,, Cheng Y,, Smalera I,, Jian W,, Goldhahn L,, Fitzgerald GA,, Funk CD . 2004. Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressure. Circulation 110 : 33603366.
151. Sousa AR,, Parikh A,, Scadding G,, Corrigan CJ,, Lee TH . 2002. Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis. N Engl J Med 347 : 14931499.
152. Devchand PR,, Keller H,, Peters JM,, Vazquez M,, Gonzalez FJ,, Wahli W . 1996. The PPARα-leukotriene B4 pathway to inflammation control. Nature 384 : 3943.
153. Krey G,, Braissant O,, L’Horset F,, Kalkhoven E,, Perroud M,, Parker MG,, Wahli W . 1997. Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol Endocrinol 11 : 779791.
154. Lin Q,, Ruuska SE,, Shaw NS,, Dong D,, Noy N . 1999. Ligand selectivity of the peroxisome proliferator-activated receptor α. Biochemistry 38 : 185190.
155. Narala VR,, Adapala RK,, Suresh MV,, Brock TG,, Peters-Golden M,, Reddy RC . 2010. Leukotriene B4 is a physiologically relevant endogenous peroxisome proliferator-activated receptor-α agonist. J Biol Chem 285 : 2206722074.
156. Borgeat P,, Naccache PH . 1990. Biosynthesis and biological activity of leukotriene B4 . Clin Biochem 23 : 459468.
157. Ott VL,, Cambier JC,, Kappler J,, Marrack P,, Swanson BJ . 2003. Mast cell-dependent migration of effector CD8+ T cells through production of leukotriene B4 . Nat Immunol 4 : 974981.
158. Woodward DF,, Krauss AH,, Nieves AL,, Spada CS . 1991. Studies on leukotriene D4 as an eosinophil chemoattractant. Drugs Exp Clin Res 17 : 543548.
159. Björk J,, Hedqvist P,, Arfors KE . 1982. Increase in vascular permeability induced by leukotriene B4 and the role of polymorphonuclear leukocytes. Inflammation 6 : 189200.
160. Dahlén SE,, Björk J,, Hedqvist P,, Arfors KE,, Hammarström S,, Lindgren JA,, Samuelsson B . 1981. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci U S A 78 : 38873891.
161. Hedqvist P,, Dahlén SE . 1983. Pulmonary and vascular effects of leukotrienes imply involvement in asthma and inflammation. Adv Prostaglandin Thromboxane Leukot Res 11 : 2732.
162. Orange RP,, Stechschulte DJ,, Austen KF . 1969. Cellular mechanisms involved in the release of slow reacting substance of anaphylaxis. Fed Proc 28 : 17101715.
163. Svensjö E . 1978. Bradykinin and prostaglandin E1, E2 and F-induced macromolecular leakage in the hamster cheek pouch. Prostaglandins Med 1 : 397410.
164. Werz O,, Steinhilber D . 2005. Development of 5-lipoxygenase inhibitors—lessons from cellular enzyme regulation. Biochem Pharmacol 70 : 327333.
165. Israel E,, Rubin P,, Kemp JP,, Grossman J,, Pierson W,, Siegel SC,, Tinkelman D,, Murray JJ,, Busse W,, Segal AT,, Fish J,, Kaiser HB,, Ledford D,, Wenzel S,, Rosenthal R,, Cohn J,, Lanni C,, Pearlman H,, Karahalios P,, Drazen JM . 1993. The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. Ann Intern Med 119 : 10591066.
166. Knorr B,, Matz J,, Bernstein JA,, Nguyen H,, Seidenberg BC,, Reiss TF,, Becker A , Pediatric Montelukast Study Group . 1998. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. JAMA 279 : 11811186.
167. Suissa S,, Dennis R,, Ernst P,, Sheehy O,, Wood-Dauphinee S . 1997. Effectiveness of the leukotriene receptor antagonist zafirlukast for mild-to-moderate asthma. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 126 : 177183.
168. Spanbroek R,, Grabner R,, Lotzer K,, Hildner M,, Urbach A,, Ruhling K,, Moos MP,, Kaiser B,, Cohnert TU,, Wahlers T,, Zieske A,, Plenz G,, Robenek H,, Salbach P,, Kuhn H,, Radmark O,, Samuelsson B,, Habenicht AJ . 2003. Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc Natl Acad Sci U S A 100 : 12381243.
169. Qiu H,, Gabrielsen A,, Agardh HE,, Wan M,, Wetterholm A,, Wong CH,, Hedin U,, Swedenborg J,, Hansson GK,, Samuelsson B,, Paulsson-Berne G,, Haeggström JZ . 2006. Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Proc Natl Acad Sci U S A 103 : 81618166.
170. Aiello RJ,, Bourassa PA,, Lindsey S,, Weng W,, Freeman A,, Showell HJ . 2002. Leukotriene B4 receptor antagonism reduces monocytic foam cells in mice. Arterioscler Thromb Vasc Biol 22 : 443449.
171. Bäck M,, Bu DX,, Bränström R,, Sheikine Y,, Yan ZQ,, Hansson GK . 2005. Leukotriene B4 signaling through NF-κB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia. Proc Natl Acad Sci U S A 102 : 1750117506.
172. Uzonyi B,, Lötzer K,, Jahn S,, Kramer C,, Hildner M,, Bretschneider E,, Radke D,, Beer M,, Vollandt R,, Evans JF,, Funk CD,, Habenicht AJ . 2006. Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate strongly correlated early genes in human endothelial cells. Proc Natl Acad Sci U S A 103 : 63266331.
173. Zhao L,, Moos MP,, Gräbner R,, Pédrono F,, Fan J,, Kaiser B,, John N,, Schmidt S,, Spanbroek R,, Lötzer K,, Huang L,, Cui J,, Rader DJ,, Evans JF,, Habenicht AJ,, Funk CD . 2004. The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Nat Med 10 : 966973.
174. Helgadottir A,, Manolescu A,, Helgason A,, Thorleifsson G,, Thorsteinsdottir U,, Gudbjartsson DF,, Gretarsdottir S,, Magnusson KP,, Gudmundsson G,, Hicks A,, Jonsson T,, Grant SF,, Sainz J,, O’Brien SJ,, Sveinbjornsdottir S,, Valdimarsson EM,, Matthiasson SE,, Levey AI,, Abramson JL,, Reilly MP,, Vaccarino V,, Wolfe ML,, Gudnason V,, Quyyumi AA,, Topol EJ,, Rader DJ,, Thorgeirsson G,, Gulcher JR,, Hakonarson H,, Kong A,, Stefansson K . 2006. A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Nat Genet 38 : 6874.
175. Helgadottir A,, Manolescu A,, Thorleifsson G,, Gretarsdottir S,, Jonsdottir H,, Thorsteinsdottir U,, Samani NJ,, Gudmundsson G,, Grant SF,, Thorgeirsson G,, Sveinbjornsdottir S,, Valdimarsson EM,, Matthiasson SE,, Johannsson H,, Gudmundsdottir O,, Gurney ME,, Sainz J,, Thorhallsdottir M,, Andresdottir M,, Frigge ML,, Topol EJ,, Kong A,, Gudnason V,, Hakonarson H,, Gulcher JR,, Stefansson K . 2004. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet 36 : 233239.
176. Kajimoto K,, Shioji K,, Ishida C,, Iwanaga Y,, Kokubo Y,, Tomoike H,, Miyazaki S,, Nonogi H,, Goto Y,, Iwai N . 2005. Validation of the association between the gene encoding 5-lipoxygenase-activating protein and myocardial infarction in a Japanese population. Circ J 69 : 10291034.
177. Hakonarson H,, Thorvaldsson S,, Helgadottir A,, Gudbjartsson D,, Zink F,, Andresdottir M,, Manolescu A,, Arnar DO,, Andersen K,, Sigurdsson A,, Thorgeirsson G,, Jonsson A,, Agnarsson U,, Bjornsdottir H,, Gottskalksson G,, Einarsson A,, Gudmundsdottir H,, Adalsteinsdottir AE,, Gudmundsson K,, Kristjansson K,, Hardarson T,, Kristinsson A,, Topol EJ,, Gulcher J,, Kong A,, Gurney M,, Thorgeirsson G,, Stefansson K . 2005. Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA 293 : 22452256.
178. Peters-Golden M,, Canetti C,, Mancuso P,, Coffey MJ . 2005. Leukotrienes: underappreciated mediators of innate immune responses. J Immunol 174 : 589594.
179. Bailie MB,, Standiford TJ,, Laichalk LL,, Coffey MJ,, Strieter R,, Peters-Golden M . 1996. Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities. J Immunol 157 : 52215224.
180. Mancuso P,, Lewis C,, Serezani CH,, Goel D,, Peters-Golden M . 2010. Intrapulmonary administration of leukotriene B4 enhances pulmonary host defense against pneumococcal pneumonia. Infect Immun 78 : 22642271.
181. Medeiros AI,, Sá-Nunes A,, Turato WM,, Secatto A,, Frantz FG,, Sorgi CA,, Serezani CH,, Deepe GS Jr,, Faccioli LH . 2008. Leukotrienes are potent adjuvant during fungal infection: effects on memory T cells. J Immunol 181 : 85448551.
182. Peres CM,, de Paula L,, Medeiros AI,, Sorgi CA,, Soares EG,, Carlos D,, Peters-Golden M,, Silva CL,, Faccioli LH . 2007. Inhibition of leukotriene biosynthesis abrogates the host control of Mycobacterium tuberculosis . Microbes Infect 9 : 483489.
183. Schultz MJ,, Wijnholds J,, Peppelenbosch MP,, Vervoordeldonk MJ,, Speelman P,, van Deventer SJ,, Borst P,, van der Poll T . 2001. Mice lacking the multidrug resistance protein 1 are resistant to Streptococcus pneumoniae-induced pneumonia. J Immunol 166 : 40594064.
184. Serezani CH,, Perrela JH,, Russo M,, Peters-Golden M,, Jancar S . 2006. Leukotrienes are essential for the control of Leishmania amazonensis infection and contribute to strain variation in susceptibility. J Immunol 177 : 32013208.
185. Serezani CH,, Aronoff DM,, Jancar S,, Mancuso P,, Peters-Golden M . 2005. Leukotrienes enhance the bactericidal activity of alveolar macrophages against Klebsiella pneumoniae through the activation of NADPH oxidase. Blood 106 : 10671075.
186. Ballinger MN,, Hubbard LL,, McMillan TR,, Toews GB,, Peters-Golden M,, Paine R III,, Moore BB . 2008. Paradoxical role of alveolar macrophage-derived granulocyte-macrophage colony-stimulating factor in pulmonary host defense post-bone marrow transplantation. Am J Physiol Lung Cell Mol Physiol 295 : L114L122.
187. Balter MS,, Toews GB,, Peters-Golden M . 1989. Multiple defects in arachidonate metabolism in alveolar macrophages from young asymptomatic smokers. J Lab Clin Med 114 : 662673.
188. Cederholm T,, Lindgren JA,, Palmblad J . 2000. Impaired leukotriene C4 generation in granulocytes from protein-energy malnourished chronically ill elderly. J Intern Med 247 : 715722.
189. Coffey MJ,, Phare SM,, Kazanjian PH,, Peters-Golden M . 1996. 5-Lipoxygenase metabolism in alveolar macrophages from subjects infected with the human immunodeficiency virus. J Immunol 157 : 393399.
190. Coffey MJ,, Wilcoxen SE,, Phare SM,, Simpson RU,, Gyetko MR,, Peters-Golden M . 1994. Reduced 5-lipoxygenase metabolism of arachidonic acid in macrophages from 1,25-dihydroxyvitamin D3-deficient rats. Prostaglandins 48 : 313329.
191. Jubiz W,, Draper RE,, Gale J,, Nolan G . 1984. Decreased leukotriene B4 synthesis by polymorphonuclear leukocytes from male patients with diabetes mellitus. Prostaglandins Leukot Med 14 : 305311.
192. Lärfars G,, Lantoine F,, Devynck MA,, Palmblad J,, Gyllenhammar H . 1999. Activation of nitric oxide release and oxidative metabolism by leukotrienes B4, C4, and D4 in human polymorphonuclear leukocytes. Blood 93 : 13991405.
193. Talvani A,, Machado FS,, Santana GC,, Klein A,, Barcelos L,, Silva JS,, Teixeira MM . 2002. Leukotriene B4 induces nitric oxide synthesis in Trypanosoma cruzi-infected murine macrophages and mediates resistance to infection. Infect Immun 70 : 42474253.
194. Flamand L,, Tremblay MJ,, Borgeat P . 2007. Leukotriene B4 triggers the in vitro and in vivo release of potent antimicrobial agents. J Immunol 178 : 80368045.
195. Powell WS,, Gravelle F,, Gravel S . 1992. Metabolism of 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid and other 5(S)-hydroxyeicosanoids by a specific dehydrogenase in human polymorphonuclear leukocytes. J Biol Chem 267 : 1923319241.
196. Graham FD,, Erlemann KR,, Gravel S,, Rokach J,, Powell WS . 2009. Oxidative stress-induced changes in pyridine nucleotides and chemoattractant 5-lipoxygenase products in aging neutrophils. Free Radic Biol Med 47 : 6271.
197. Powell WS,, Gravelle F,, Gravel S . 1994. Phorbol myristate acetate stimulates the formation of 5-oxo-6,8,11,14-eicosatetraenoic acid by human neutrophils by activating NADPH oxidase. J Biol Chem 269 : 2537325380.
198. Cossette C,, Patel P,, Anumolu JR,, Sivendran S,, Lee GJ,, Gravel S,, Graham FD,, Lesimple A,, Mamer OA,, Rokach J,, Powell WS . 2008. Human neutrophils convert the sebum-derived polyunsaturated fatty acid sebaleic acid to a potent granulocyte chemoattractant. J Biol Chem 283 : 1123411243.
199. Patel P,, Cossette C,, Anumolu JR,, Gravel S,, Lesimple A,, Mamer OA,, Rokach J,, Powell WS . 2008. Structural requirements for activation of the 5-oxo-6E,8Z, 11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) receptor: identification of a mead acid metabolite with potent agonist activity. J Pharmacol Exp Ther 325 : 698707.
200. Powell WS,, Chung D,, Gravel S . 1995. 5-Oxo-6,8,11,14-eicosatetraenoic acid is a potent stimulator of human eosinophil migration. J Immunol 154 : 41234132.
201. Powell WS,, Rokach J . 2005. Biochemistry, biology and chemistry of the 5-lipoxygenase product 5-oxo-ETE. Prog Lipid Res 44 : 154183.
202. Brink CB,, Harvey BH,, Bodenstein J,, Venter DP,, Oliver DW . 2004. Recent advances in drug action and therapeutics: relevance of novel concepts in G-protein-coupled receptor and signal transduction pharmacology. Br J Clin Pharmacol 57 : 373387.
203. Takeda S,, Kadowaki S,, Haga T,, Takaesu H,, Mitaku S . 2002. Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett 520 : 97101.
204. Hosoi T,, Koguchi Y,, Sugikawa E,, Chikada A,, Ogawa K,, Tsuda N,, Suto N,, Tsunoda S,, Taniguchi T,, Ohnuki T . 2002. Identification of a novel human eicosanoid receptor coupled to Gi/o . J Biol Chem 277 : 3145931465.
205. Jones CE,, Holden S,, Tenaillon L,, Bhatia U,, Seuwen K,, Tranter P,, Turner J,, Kettle R,, Bouhelal R,, Charlton S,, Nirmala NR,, Jarai G,, Finan P . 2003. Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils. Mol Pharmacol 63 : 471477.
206. Norgauer J,, Barbisch M,, Czech W,, Pareigis J,, Schwenk U,, Schröder JM . 1996. Chemotactic 5-oxo-icosatetraenoic acids activate a unique pattern of neutrophil responses. Analysis of phospholipid metabolism, intracellular Ca2+ transients, actin reorganization, superoxide-anion production and receptor up-regulation. Eur J Biochem 236 : 10031009.
207. O’Flaherty JT,, Kuroki M,, Nixon AB,, Wijkander J,, Yee E,, Lee SL,, Smitherman PK,, Wykle RL,, Daniel LW . 1996. 5-Oxo-eicosanoids and hematopoietic cytokines cooperate in stimulating neutrophil function and the mitogen-activated protein kinase pathway. J Biol Chem 271 : 1782117828.
208. Hosoi T,, Sugikawa E,, Chikada A,, Koguchi Y,, Ohnuki T . 2005. TG1019/OXE, a Gαi/o-protein-coupled receptor, mediates 5-oxo-eicosatetraenoic acid-induced chemotaxis. Biochem Biophys Res Commun 334 : 987995.
209. O’Flaherty JT,, Rogers LC,, Chadwell BA,, Owen JS,, Rao A,, Cramer SD,, Daniel LW . 2002. 5(S)-Hydroxy-6,8,11,14-E,Z,Z,Z-eicosatetraenoate stimulates PC3 cell signaling and growth by a receptor-dependent mechanism. Cancer Res