Lipoxins, Resolvins, and the Resolution of Inflammation

  • Antonio Recchiuti
  • Eleonora Cianci
  • Felice Simiele
  • Mario RomanoEmail author
Part of the Progress in Inflammation Research book series (PIR)


Resolution of acute inflammation is an active process, where endogenous specialized pro-resolving mediators (SPM), derived from polyunsaturated fatty acids via lipoxygenase (LO)-driven biochemical pathways, have pivotal roles in “turning off” pro-inflammatory signals, prompting timely resolution. SPM potent and stereospecific bioactions are of considerable interest in immunopharmacology since unresolved inflammation represents a key pathogenetic mechanism of several widespread diseases.

In recent years, biosynthetic routes, chemical structure, and specific G-protein coupled receptors for many members of the SPM genus have been uncovered. This knowledge, that emphasizes the complex pathobiological role of LO in resolution of inflammation, provides previously unforeseen opportunity and strategies for innovative pharmacology for a variety of human pathologies.

Here, we provide an overview of biosynthetic pathways, receptors, bioactions and underlying mechanisms as well as of preclinical and clinical evidence of efficacy of the best-studied SPM.


Chronic diseases Enzymes G-protein coupled receptors Immunity Immunoresolvent Lipoxygenases Leukocytes Polyunsaturated fatty acids 

List of Abbreviations


Arachidonic acid (5Z, 8Z, 11Z, 14Z -eicosatetraenoic acid)


Acute kidney injury


Acute lung injury


Lipoxin A4 receptor/formyl peptide receptor 2


Aspirin triggered lipoxin


Aspirin triggered lipoxin analog


C-C Chemokine receptor type 5


Cyclooxygenase (prostaglandin H2 synthase)


Docosahexaenoic acid (4Z, 7Z, 10Z, 13Z, 16Z, 19Z -docosahexaenoic acid)


Eicosapentaenoic acid (5Z, 8Z, 11Z, 14Z, 17Z -eicosapentaenoic acid)


G-Protein coupled receptor 32/resolvin D1 receptor 1


Herpes simplex virus








Lipid mediator








Monocyte chemotactic protein 1


Nitric oxide




Platelet-derived growth factor




Polyunsaturated fatty




Type 2 diabetes


Temporomandibular joint


Tumor necrosis factor-α


Vascular smooth muscle cells


  1. 1.
    Majno G, Joris I (2004) Cells, tissues, and disease: principles of general pathology: principles of general pathology. Oxford University Press, USAGoogle Scholar
  2. 2.
    Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454(7203):428–435PubMedCrossRefGoogle Scholar
  3. 3.
    Gordon S (2007) The macrophage: past, present and future. Eur J Immunol 37(Suppl 1):S9–17PubMedCrossRefGoogle Scholar
  4. 4.
    Serhan CN, Brain SD, Buckley CD, Gilroy DW, Haslett C, O’Neill LA, Perretti M, Rossi AG, Wallace JL (2007) Resolution of inflammation: state of the art, definitions and terms. FASEB J 21(2):325–332PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, Hong S, Serhan CN (2005) Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 174(7):4345–4355PubMedCrossRefGoogle Scholar
  6. 6.
    Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8(5):349–361PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Haworth O, Cernadas M, Yang R, Serhan CN, Levy BD (2008) Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat Immunol 9(8):873–879PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Navarro-Xavier RA, Newson J, Silveira VL, Farrow SN, Gilroy DW, Bystrom J (2009) A new strategy for the identification of novel molecules with targeted proresolution of inflammation properties. J Immunol 184(3):1516–1525PubMedCrossRefGoogle Scholar
  9. 9.
    Recchiuti A, Codagnone M, Pierdomenico AM, Rossi C, Mari VC, Cianci E, Simiele F, Gatta V, Romano M (2014) Immunoresolving actions of oral resolvin D1 include selective regulation of the transcription machinery in resolution-phase mouse macrophages. FASEB J 28(7):3090–3102PubMedCrossRefGoogle Scholar
  10. 10.
    Schwab JM, Chiang N, Arita M, Serhan CN (2007) Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447(7146):869–874PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN (2001) Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2(7):612–619PubMedCrossRefGoogle Scholar
  12. 12.
    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(8):1197–1204PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Serhan CN, Hamberg M, Samuelsson B (1984) Lipoxins: Novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc Natl Acad Sci USA 81(17):5335–5339PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    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(3):943–949PubMedCrossRefGoogle Scholar
  15. 15.
    Chiang N, Bermudez EA, Ridker PM, Hurwitz S, Serhan CN (2004) Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci USA 101(42):15178–15183PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Dalli J, Colas RA, Serhan CN (2013) Novel n-3 immunoresolvents: structures and actions. Sci Rep 3:1940PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Dalli J, Winkler JW, Colas RA, Arnardottir H, Cheng CY, Chiang N, Petasis NA, Serhan CN (2013) Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents. Chem Biol 20(2):188–201PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Serhan CN, Chiang N (2013) Resolution phase lipid mediators of inflammation: agonists of resolution. Curr Opin Pharmacol 13(4):632–640PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Kasuga K, Yang R, Porter TF, Agrawal N, Petasis NA, Irimia D, Toner M, Serhan CN (2008) Rapid appearance of resolvin precursors in inflammatory exudates: novel mechanisms in resolution. J Immunol 181(12):8677–8687PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Colas RA, Shinohara M, Dalli J, Chiang N, Serhan CN (2014) Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. Am J Physiol Cell Physiol 307(1):C39–C54PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Psychogios N, Hau DD, Peng J, Guo AC, Mandal R, Bouatra S, Sinelnikov I, Krishnamurthy R, Eisner R, Gautam B, Young N, Xia J, Knox C, Dong E, Huang P, Hollander Z, Pedersen TL, Smith SR, Bamforth F, Greiner R, McManus B, Newman JW, Goodfriend T, Wishart DS (2011) The human serum metabolome. PLoS One 6(2), e16957PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Weiss GA, Troxler H, Klinke G, Rogler D, Braegger C, Hersberger M (2013) High levels of anti-inflammatory and pro-resolving lipid mediators lipoxins and resolvins and declining docosahexaenoic acid levels in human milk during the first month of lactation. Lipids Health Dis 12:89PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Gangemi S, Luciotti G, D’Urbano E, Mallamace A, Santoro D, Bellinghieri G, Davi G, Romano M (2003) Physical exercise increases urinary excretion of lipoxin A4 and related compounds. J Appl Physiol (1985) 94(6):2237–2240CrossRefGoogle Scholar
  24. 24.
    Markworth JF, Vella L, Lingard BS, Tull DL, Rupasinghe TW, Sinclair AJ, Maddipati KR, Cameron-Smith D (2013) Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment. Am J Physiol Regul Integr Comp Physiol 305(11):R1281–R1296PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Edenius C, Kumlin M, Bjork T, Anggard A, Lindgren JA (1990) Lipoxin formation in human nasal polyps and bronchial tissue. FEBS Lett 272(1–2):25–28PubMedCrossRefGoogle Scholar
  26. 26.
    Frediani JK, Jones DP, Tukvadze N, Uppal K, Sanikidze E, Kipiani M, Tran VT, Hebbar G, Walker DI, Kempker RR, Kurani SS, Colas RA, Dalli J, Tangpricha V, Serhan CN, Blumberg HM, Ziegler TR (2014) Plasma metabolomics in human pulmonary tuberculosis disease: a pilot study. PLoS One 9(10), e108854PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Brezinski DA, Nesto RW, Serhan CN (1992) Angioplasty triggers intracoronary leukotrienes and lipoxin A4. Impact of aspirin therapy. Circulation 86(1):56–63PubMedCrossRefGoogle Scholar
  28. 28.
    Chiang N, Shinohara M, Dalli J, Mirakaj V, Kibi M, Choi AMK, Serhan CN (2013) Inhaled carbon monoxide accelerates resolution of inflammation via unique proresolving mediator–heme oxygenase-1 circuits. J Immunol 190(12):6378–6388PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Pillai PS, Leeson S, Porter TF, Owens CD, Kim JM, Conte MS, Serhan CN, Gelman S (2012) Chemical mediators of inflammation and resolution in post-operative abdominal aortic aneurysm patients. Inflammation 35(1):98–113PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Serhan CN, Hamberg M, Samuelsson B, Morris J, Wishka DG (1986) On the stereochemistry and biosynthesis of lipoxin B. Proc Natl Acad Sci USA 83(7):1983–1987PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Serhan CN, Hirsch U, Palmblad J, Samuelsson B (1987) Formation of lipoxin A by granulocytes from eosinophilic donors. FEBS Lett 217(2):242–246PubMedCrossRefGoogle Scholar
  32. 32.
    Levy BD, Romano M, Chapman HA, Reilly JJ, Drazen J, Serhan CN (1993) Human alveolar macrophages have 15-lipoxygenase and generate 15(S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid and lipoxins. J Clin Invest 92(3):1572–1579PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Munger KA, Montero A, Fukunaga M, Uda S, Yura T, Imai E, Kaneda Y, Valdivielso JM, Badr KF (1999) Transfection of rat kidney with human 15-lipoxygenase suppresses inflammation and preserves function in experimental glomerulonephritis. Proc Natl Acad Sci USA 96(23):13375–13380PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Planaguma A, Kazani S, Marigowda G, Haworth O, Mariani TJ, Israel E, Bleecker ER, Curran-Everett D, Erzurum SC, Calhoun WJ, Castro M, Chung KF, Gaston B, Jarjour NN, Busse WW, Wenzel SE, Levy BD (2008) Airway lipoxin A4 generation and lipoxin A4 receptor expression are decreased in severe asthma. Am J Respir Crit Care Med 178(6):574–582PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Edenius C, Haeggstrom J, Lindgren JA (1988) Transcellular conversion of endogenous arachidonic acid to lipoxins in mixed human platelet-granulocyte suspensions. Biochem Biophys Res Commun 157(2):801–807PubMedCrossRefGoogle Scholar
  36. 36.
    Fiore S, Serhan CN (1990) Formation of lipoxins and leukotrienes during receptor-mediated interactions of human platelets and recombinant human granulocyte/macrophage colony-stimulating factor-primed neutrophils. J Exp Med 172(5):1451–1457PubMedCrossRefGoogle Scholar
  37. 37.
    Serhan CN, Sheppard KA, Fiore S (1990) Lipoxin formation: evaluation of the role and actions of leukotriene A4. Adv Prostaglandin Thromboxane Leukot Res 20:54–62PubMedGoogle Scholar
  38. 38.
    Sheppard KA, Greenberg SM, Funk CD, Romano M, Serhan CN (1992) Lipoxin generation by human megakaryocyte-induced 12-lipoxygenase. Biochim Biophys Acta 1133(2):223–234PubMedCrossRefGoogle Scholar
  39. 39.
    Romano M, Serhan CN (1992) Lipoxin generation by permeabilized human platelets. Biochemistry 31(35):8269–8277PubMedCrossRefGoogle Scholar
  40. 40.
    Romano M, Chen XS, Takahashi Y, Yamamoto S, Funk CD, Serhan CN (1993) Lipoxin synthase activity of human platelet 12-lipoxygenase. Biochem J 296(Pt 1):127–133PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Mattoscio D, Evangelista V, De Cristofaro R, Recchiuti A, Pandolfi A, Di Silvestre S, Manarini S, Martelli N, Rocca B, Petrucci G, Angelini DF, Battistini L, Robuffo I, Pensabene T, Pieroni L, Furnari ML, Pardo F, Quattrucci S, Lancellotti S, Davi G, Romano M (2010) Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: impact on mediators and mechanisms of the inflammatory response. FASEB J 24(10):3970–3980PubMedCrossRefGoogle Scholar
  42. 42.
    Claria J, Serhan CN (1995) Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci USA 92(21):9475–9479PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Claria J, Lee MH, Serhan CN (1996) Aspirin-triggered lipoxins (15-epi-LX) are generated by the human lung adenocarcinoma cell line (A549)-neutrophil interactions and are potent inhibitors of cell proliferation. Mol Med 2(5):583–596PubMedGoogle Scholar
  44. 44.
    Titos E, Chiang N, Serhan CN, Romano M, Gaya J, Pueyo G, Claria J (1999) Hepatocytes are a rich source of novel aspirin-triggered 15-epi-lipoxin A(4). Am J Physiol 277(5 Pt 1):C870–C877PubMedGoogle Scholar
  45. 45.
    Brezinski DA, Serhan CN (1991) Characterization of lipoxins by combined gas chromatography and electron-capture negative ion chemical ionization mass spectrometry: formation of lipoxin A4 by stimulated human whole blood. Biol Mass Spectrom 20(2):45–52PubMedCrossRefGoogle Scholar
  46. 46.
    Sanak M, Levy BD, Clish CB, Chiang N, Gronert K, Mastalerz L, Serhan CN, Szczeklik A (2000) Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant asthmatics. Eur Respir J 16(1):44–49PubMedCrossRefGoogle Scholar
  47. 47.
    Fiorucci S, Santucci L, Wallace JL, Sardina M, Romano M, del Soldato P, Morelli A (2003) Interaction of a selective cyclooxygenase-2 inhibitor with aspirin and NO-releasing aspirin in the human gastric mucosa. Proc Natl Acad Sci USA 100(19):10937–10941PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Calder PC (2013) n-3 fatty acids, inflammation and immunity: new mechanisms to explain old actions. Proc Nutr Soc 72(3):326–336PubMedCrossRefGoogle Scholar
  49. 49.
    De Caterina R (2011) n-3 fatty acids in cardiovascular disease. N Engl J Med 364(25):2439–2450PubMedCrossRefGoogle Scholar
  50. 50.
    Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico (1999). Lancet 354 (9177): 447–455Google Scholar
  51. 51.
    Iigo M, Nakagawa T, Ishikawa C, Iwahori Y, Asamoto M, Yazawa K, Araki E, Tsuda H (1997) Inhibitory effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung. Br J Cancer 75(5):650–655PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    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(17):14677–14687PubMedCrossRefGoogle Scholar
  53. 53.
    Perretti M, Chiang N, La M, Fierro IM, Marullo S, Getting SJ, Solito E, Serhan CN (2002) Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nat Med 8(11):1296–1302PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, Yang R, Colgan SP, Petasis NA (2006) Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol 176(3):1848–1859PubMedCrossRefGoogle Scholar
  55. 55.
    Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN (2005) Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 201(5):713–722PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Tjonahen E, Oh SF, Siegelman J, Elangovan S, Percarpio KB, Hong S, Arita M, Serhan CN (2006) Resolvin E2: identification and anti-inflammatory actions: pivotal role of human 5-lipoxygenase in resolvin E series biosynthesis. Chem Biol 13(11):1193–1202PubMedCrossRefGoogle Scholar
  57. 57.
    Haas-Stapleton EJ, Lu Y, Hong S, Arita M, Favoreto S, Nigam S, Serhan CN, Agabian N (2007) Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator resolvin E1. PLoS One 2(12), e1316PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Ogawa N, Kobayashi Y (2009) Total synthesis of resolvin E1. Tetrahedron Lett 50(44):6079–6082CrossRefGoogle Scholar
  59. 59.
    Oh SF, Dona M, Fredman G, Krishnamoorthy S, Irimia D, Serhan CN (2012) Resolvin e2 formation and impact in inflammation resolution. J Immunol 188(9):4527–4534PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Isobe Y, Arita M, Iwamoto R, Urabe D, Todoroki H, Masuda K, Inoue M, Arai H (2013) Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3. J Biochem 153(4):355–360PubMedCrossRefGoogle Scholar
  61. 61.
    Isobe Y, Arita M, Matsueda S, Iwamoto R, Fujihara T, Nakanishi H, Taguchi R, Masuda K, Sasaki K, Urabe D, Inoue M, Arai H (2012) Identification and structure determination of novel anti-inflammatory mediator resolvin E3, 17,18-dihydroxyeicosapentaenoic acid. J Biol Chem 287(13):10525–10534PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Yokokura Y, Isobe Y, Matsueda S, Iwamoto R, Goto T, Yoshioka T, Urabe D, Inoue M, Arai H, Arita M (2014) Identification of 14,20-dihydroxy-docosahexaenoic acid as a novel anti-inflammatory metabolite. J Biochem 156(6):315–321PubMedCrossRefGoogle Scholar
  63. 63.
    Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac R-L (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(8):1025–1037PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Spite M, Norling LV, Summers L, Yang R, Cooper D, Petasis NA, Flower RJ, Perretti M, Serhan CN (2009) Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature 461(7268):1287–1291PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Chiang N, Fredman G, Backhed F, Oh SF, Vickery T, Schmidt BA, Serhan CN (2012) Infection regulates pro-resolving mediators that lower antibiotic requirements. Nature 484(7395):524–528PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Winkler JW, Uddin J, Serhan CN, Petasis NA (2013) Stereocontrolled total synthesis of the potent anti-inflammatory and pro-resolving lipid mediator resolvin D3 and its aspirin-triggered 17R-epimer. Org Lett 15(7):1424–1427PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    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(44):43807–43817PubMedCrossRefGoogle Scholar
  68. 68.
    Ishida T, Yoshida M, Arita M, Nishitani Y, Nishiumi S, Masuda A, Mizuno S, Takagawa T, Morita Y, Kutsumi H, Inokuchi H, Serhan CN, Blumberg RS, Azuma T (2009) Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis. Inflamm Bowel Dis 16(1):87–95CrossRefGoogle Scholar
  69. 69.
    Dalli J, Zhu M, Vlasenko NA, Deng B, Haeggstrom JZ, Petasis NA, Serhan CN (2013) The novel 13S,14S-epoxy-maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A4 hydrolase (LTA4H), and shifts macrophage phenotype. FASEB J 27(7):2573–2583PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Serhan CN, Dalli J, Karamnov S, Choi A, Park CK, Xu ZZ, Ji RR, Zhu M, Petasis NA (2012) Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. FASEB J 26(4):1755–1765PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M (2009) Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 206(1):15–23PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Deng B, Wang CW, Arnardottir HH, Li Y, Cheng CY, Dalli J, Serhan CN (2014) Maresin biosynthesis and identification of maresin 2, a new anti-inflammatory and pro-resolving mediator from human macrophages. PLoS One 9(7), e102362PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Bandeira-Melo C, Serra MF, Diaz BL, Cordeiro RS, Silva PM, Lenzi HL, Bakhle YS, Serhan CN, Martins MA (2000) Cyclooxygenase-2-derived prostaglandin E2 and lipoxin A4 accelerate resolution of allergic edema in Angiostrongylus costaricensis-infected rats: relationship with concurrent eosinophilia. J Immunol 164(2):1029–1036PubMedCrossRefGoogle Scholar
  74. 74.
    Soyombo O, Spur BW, Lee TH (1994) Effects of lipoxin A4 on chemotaxis and degranulation of human eosinophils stimulated by platelet-activating factor and N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Allergy 49(4):230–234PubMedCrossRefGoogle Scholar
  75. 75.
    Carlo T, Kalwa H, Levy BD (2013) 15-Epi-lipoxin A4 inhibits human neutrophil superoxide anion generation by regulating polyisoprenyl diphosphate phosphatase 1. FASEB J 27(7):2733–2741PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Colgan SP, Serhan CN, Parkos CA, Delp-Archer C, Madara JL (1993) Lipoxin A4 modulates transmigration of human neutrophils across intestinal epithelial monolayers. J Clin Invest 92(1):75–82PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Fierro IM, Colgan SP, Bernasconi G, Petasis NA, Clish CB, Arita M, Serhan CN (2003) Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit human neutrophil migration: comparisons between synthetic 15 epimers in chemotaxis and transmigration with microvessel endothelial cells and epithelial cells. J Immunol 170(5):2688–2694PubMedCrossRefGoogle Scholar
  78. 78.
    Scalia R, Gefen J, Petasis NA, Serhan CN, Lefer AM (1997) Lipoxin A4 stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: role of P-selectin. Proc Natl Acad Sci USA 94(18):9967–9972PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Gewirtz AT, Fokin VV, Petasis NA, Serhan CN, Madara JL (1999) LXA4, aspirin-triggered 15-epi-LXA4, and their analogs selectively downregulate PMN azurophilic degranulation. Am J Physiol 276(4 Pt 1):C988–C994PubMedGoogle Scholar
  80. 80.
    Jozsef L, Zouki C, Petasis NA, Serhan CN, Filep JG (2002) Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit peroxynitrite formation, NF-kappa B and AP-1 activation, and IL-8 gene expression in human leukocytes. Proc Natl Acad Sci USA 99(20):13266–13271PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Godson C, Mitchell S, Harvey K, Petasis NA, Hogg N, Brady HR (2000) Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol 164(4):1663–1667PubMedCrossRefGoogle Scholar
  82. 82.
    Maddox JF, Serhan CN (1996) Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion: selective inactivation by dehydrogenation and reduction. J Exp Med 183(1):137–146PubMedCrossRefGoogle Scholar
  83. 83.
    Prescott D, McKay DM (2011) Aspirin-triggered lipoxin enhances macrophage phagocytosis of bacteria while inhibiting inflammatory cytokine production. Am J Physiol Gastrointest Liver Physiol 301(3):G487–G497PubMedCrossRefGoogle Scholar
  84. 84.
    Romano M, Maddox JF, Serhan CN (1996) Activation of human monocytes and the acute monocytic leukemia cell line (THP-1) by lipoxins involves unique signaling pathways for lipoxin A4 versus lipoxin B4: evidence for differential Ca2+ mobilization. J Immunol 157(5):2149–2154PubMedGoogle Scholar
  85. 85.
    Ramon S, Bancos S, Serhan CN, Phipps RP (2013) Lipoxin A modulates adaptive immunity by decreasing memory B-cell responses via an ALX/FPR2-dependent mechanism. Eur J Immunol 44(2):357–369CrossRefGoogle Scholar
  86. 86.
    Borgeson E, Lonn J, Bergstrom I, Brodin VP, Ramstrom S, Nayeri F, Sarndahl E, Bengtsson T (2011) Lipoxin A(4) inhibits porphyromonas gingivalis-induced aggregation and reactive oxygen species production by modulating neutrophil-platelet interaction and CD11b expression. Infect Immun 79(4):1489–1497PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Fiore S, Serhan CN (1995) Lipoxin A4 receptor activation is distinct from that of the formyl peptide receptor in myeloid cells: inhibition of CD11/18 expression by lipoxin A4-lipoxin A4 receptor interaction. Biochemistry 34(51):16678–16686PubMedCrossRefGoogle Scholar
  88. 88.
    Levy BD, Fokin VV, Clark JM, Wakelam MJ, Petasis NA, Serhan CN (1999) Polyisoprenyl phosphate (PIPP) signaling regulates phospholipase D activity: a ‘stop’ signaling switch for aspirin-triggered lipoxin A4. FASEB J 13(8):903–911PubMedGoogle Scholar
  89. 89.
    Papayianni A, Serhan CN, Brady HR (1996) Lipoxin A4 and B4 inhibit leukotriene-stimulated interactions of human neutrophils and endothelial cells. J Immunol 156(6):2264–2272PubMedGoogle Scholar
  90. 90.
    Serhan CN, Maddox JF, Petasis NA, Akritopoulou-Zanze I, Papayianni A, Brady HR, Colgan SP, Madara JL (1995) Design of lipoxin A4 stable analogs that block transmigration and adhesion of human neutrophils. Biochemistry 34(44):14609–14615PubMedCrossRefGoogle Scholar
  91. 91.
    Maddox JF, Hachicha M, Takano T, Petasis NA, Fokin VV, Serhan CN (1997) Lipoxin A4 stable analogs are potent mimetics that stimulate human monocytes and THP-1 cells via a G-protein-linked lipoxin A4 receptor. J Biol Chem 272(11):6972–6978PubMedCrossRefGoogle Scholar
  92. 92.
    Mitchell D, O’Meara SJ, Gaffney A, Crean JKG, Kinsella BT, Godson C (2007) The lipoxin A4 receptor is coupled to SHP-2 activation: implications for regulation of receptor tyrosine kinases. J Biol Chem 282(21):15606–15618PubMedCrossRefGoogle Scholar
  93. 93.
    Levy BD, De Sanctis GT, Devchand PR, Kim E, Ackerman K, Schmidt BA, Szczeklik W, Drazen JM, Serhan CN (2002) Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4). Nat Med 8(9):1018–1023PubMedCrossRefGoogle Scholar
  94. 94.
    Ariel A, Chiang N, Arita M, Petasis NA, Serhan CN (2003) Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-alpha secretion from human T cells. J Immunol 170(12):6266–6272PubMedCrossRefGoogle Scholar
  95. 95.
    Ariel A, Fredman G, Sun Y-P, 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(11):1209–1216PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Barnig C, Cernadas M, Dutile S, Liu X, Perrella MA, Kazani S, Wechsler ME, Israel E, Levy BD (2013) Lipoxin A4 regulates natural killer cell and type 2 innate lymphoid cell activation in asthma. Sci Transl Med 5(174):174ra126CrossRefGoogle Scholar
  97. 97.
    Ramstedt U, Ng J, Wigzell H, Serhan CN, Samuelsson B (1985) Action of novel eicosanoids lipoxin A and B on human natural killer cell cytotoxicity: effects on intracellular cAMP and target cell binding. J Immunol 135(5):3434–3438PubMedGoogle Scholar
  98. 98.
    Ramstedt U, Serhan CN, Nicolaou KC, Webber SE, Wigzell H, Samuelsson B (1987) Lipoxin A-induced inhibition of human natural killer cell cytotoxicity: studies on stereospecificity of inhibition and mode of action. J Immunol 138(1):266–270PubMedGoogle Scholar
  99. 99.
    Brezinski ME, Gimbrone MA Jr, Nicolaou KC, Serhan CN (1989) Lipoxins stimulate prostacyclin generation by human endothelial cells. FEBS Lett 245(1–2):167–172PubMedCrossRefGoogle Scholar
  100. 100.
    Cezar-de-Mello PF, Nascimento-Silva V, Villela CG, Fierro IM (2006) Aspirin-triggered Lipoxin A4 inhibition of VEGF-induced endothelial cell migration involves actin polymerization and focal adhesion assembly. Oncogene 25(1):122–129PubMedGoogle Scholar
  101. 101.
    Cezar-de-Mello PF, Vieira AM, Nascimento-Silva V, Villela CG, Barja-Fidalgo C, Fierro IM (2008) ATL-1, an analogue of aspirin-triggered lipoxin A4, is a potent inhibitor of several steps in angiogenesis induced by vascular endothelial growth factor. Br J Pharmacol 153(5):956–965PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Fierro IM, Kutok JL, Serhan CN (2002) Novel lipid mediator regulators of endothelial cell proliferation and migration: aspirin-triggered-15R-lipoxin A(4) and lipoxin A(4). J Pharmacol Exp Ther 300(2):385–392PubMedCrossRefGoogle Scholar
  103. 103.
    Morris T, Stables M, Hobbs A, de Souza P, Colville-Nash P, Warner T, Newson J, Bellingan G, Gilroy DW (2009) Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol 183(3):2089–2096PubMedCrossRefGoogle Scholar
  104. 104.
    Nascimento-Silva V, Arruda MA, Barja-Fidalgo C, Fierro IM (2007) Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: a novel antioxidative mechanism. Thromb Haemost 97(1):88–98PubMedGoogle Scholar
  105. 105.
    Nascimento-Silva V, Arruda MA, Barja-Fidalgo C, Villela CG, Fierro IM (2005) Novel lipid mediator aspirin-triggered lipoxin A4 induces heme oxygenase-1 in endothelial cells. Am J Physiol Cell Physiol 289(3):C557–C563PubMedCrossRefGoogle Scholar
  106. 106.
    Bonnans C, Fukunaga K, Levy MA, Levy BD (2006) Lipoxin A(4) regulates bronchial epithelial cell responses to acid injury. Am J Pathol 168(4):1064–1072PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Buchanan PJ, McNally P, Harvey BJ, Urbach V (2013) Lipoxin A4-mediated KATP potassium channel activation results in cystic fibrosis airway epithelial repair. Am J Physiol Lung Cell Mol Physiol 305(2):L193–L201PubMedCrossRefGoogle Scholar
  108. 108.
    Grumbach Y, Quynh NV, Chiron R, Urbach V (2009) LXA4 stimulates ZO-1 expression and transepithelial electrical resistance in human airway epithelial (16HBE14o-) cells. Am J Physiol Lung Cell Mol Physiol 296(1):L101–L108PubMedCrossRefGoogle Scholar
  109. 109.
    Ho KJ, Spite M, Owens CD, Lancero H, Kroemer AH, Pande R, Creager MA, Serhan CN, Conte MS (2010) Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol 177(4):2116–2123PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Petri MH, Laguna-Fernandez A, Tseng CN, Hedin U, Perretti M, Back M (2014) Aspirin-triggered 15-epi-lipoxin A4 signals through FPR2/ALX in vascular smooth muscle cells and protects against intimal hyperplasia after carotid ligation. Int J Cardiol 179:370–372PubMedCrossRefGoogle Scholar
  111. 111.
    Sodin-Semrl S, Taddeo B, Tseng D, Varga J, Fiore S (2000) Lipoxin A4 inhibits IL-1 beta-induced IL-6, IL-8, and matrix metalloproteinase-3 production in human synovial fibroblasts and enhances synthesis of tissue inhibitors of metalloproteinases. J Immunol 164(5):2660–2666PubMedCrossRefGoogle Scholar
  112. 112.
    Wu SH, Wu XH, Lu C, Dong L, Chen ZQ (2006) Lipoxin A4 inhibits proliferation of human lung fibroblasts induced by connective tissue growth factor. Am J Respir Cell Mol Biol 34(1):65–72PubMedCrossRefGoogle Scholar
  113. 113.
    McMahon B, Mitchell D, Shattock R, Martin F, Brady HR, Godson C (2002) Lipoxin, leukotriene, and PDGF receptors cross-talk to regulate mesangial cell proliferation. FASEB J 16(13):1817–1819PubMedGoogle Scholar
  114. 114.
    Mitchell D, Rodgers K, Hanly J, McMahon B, Brady HR, Martin F, Godson C (2004) Lipoxins inhibit Akt/PKB activation and cell cycle progression in human mesangial cells. Am J Pathol 164(3):937–946PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Rodgers K, McMahon B, Mitchell D, Sadlier D, Godson C (2005) Lipoxin A4 modifies platelet-derived growth factor-induced pro-fibrotic gene expression in human renal mesangial cells. Am J Pathol 167(3):683–694PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Arita M, Ohira T, Sun Y-P, Elangovan S, Chiang N, Serhan CN (2007) Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J Immunol 178(6):3912–3917PubMedCrossRefGoogle Scholar
  117. 117.
    Campbell EL, Louis NA, Tomassetti SE, Canny GO, Arita M, Serhan CN, Colgan SP (2007) Resolvin E1 promotes mucosal surface clearance of neutrophils: a new paradigm for inflammatory resolution. FASEB J 21(12):3162–3170PubMedCrossRefGoogle Scholar
  118. 118.
    Dona M, Fredman G, Schwab JM, Chiang N, Arita M, Goodarzi A, Cheng G, von Andrian UH, Serhan CN (2008) Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood 112(3):848–855PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Fredman G, Van Dyke TE, Serhan CN (2010) Resolvin E1 regulates adenosine diphosphate activation of human platelets. Arterioscler Thromb Vasc Biol 30(10):2005–2013PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Herrera BS, Ohira T, Gao L, Omori K, Yang R, Zhu M, Muscara MN, Serhan CN, Van Dyke TE, Gyurko R (2008) An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption. Br J Pharmacol 155(8):1214–1223PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Zhu M, Van Dyke TE, Gyurko R (2013) Resolvin E1 regulates osteoclast fusion via DC-STAMP and NFATc1. FASEB J 27(8):3344–3353PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Sun YP, Oh SF, Uddin J, Yang R, Gotlinger K, Campbell E, Colgan SP, Petasis NA, Serhan CN (2007) Resolvin D1 and its aspirin-triggered 17R epimer. Stereochemical assignments, anti-inflammatory properties, and enzymatic inactivation. J Biol Chem 282(13):9323–9334PubMedCrossRefGoogle Scholar
  123. 123.
    Krishnamoorthy S, Recchiuti A, Chiang N, Fredman G, Serhan CN (2012) Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs. Am J Pathol 180(5):2018–2027PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Krishnamoorthy S, Recchiuti A, Chiang N, Yacoubian S, Lee CH, Yang R, Petasis NA, Serhan CN (2010) Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci USA 107(4):1660–1665PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Recchiuti A, Krishnamoorthy S, Fredman G, Chiang N, Serhan CN (2011) MicroRNAs in resolution of acute inflammation: identification of novel resolvin D1-miRNA circuits. FASEB J 25(2):544–560PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Norling LV, Dalli J, Flower RJ, Serhan CN, Perretti M (2012) Resolvin D1 limits polymorphonuclear leukocytes recruitment to inflammatory loci: receptor-dependent actions. Arterioscler Thromb Vasc Biol 32(8):1970–1978Google Scholar
  127. 127.
    Miyahara T, Runge S, Chatterjee A, Chen M, Mottola G, Fitzgerald JM, Serhan CN, Conte MS (2013) D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury. FASEB J 27(6):2220–2232PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Mustafa M, Zarrough A, Bolstad AI, Lygre H, Mustafa K, Hasturk H, Serhan C, Kantarci A, Van Dyke TE (2013) Resolvin D1 protects periodontal ligament. Am J Physiol Cell Physiol 305(6):C673–C679PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Ramon S, Gao F, Serhan CN, Phipps RP (2012) Specialized proresolving mediators enhance human B cell differentiation to antibody-secreting cells. J Immunol 189(2):1036–1042PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Hsiao HM, Sapinoro RE, Thatcher TH, Croasdell A, Levy EP, Fulton RA, Olsen KC, Pollock SJ, Serhan CN, Phipps RP, Sime PJ (2013) A novel anti-inflammatory and pro-resolving role for resolvin D1 in acute cigarette smoke-induced lung inflammation. PLoS One 8(3), e58258PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Clish CB, Levy BD, Chiang N, Tai HH, Serhan CN (2000) Oxidoreductases in lipoxin A4 metabolic inactivation: a novel role for 15-onoprostaglandin 13-reductase/leukotriene B4 12-hydroxydehydrogenase in inflammation. J Biol Chem 275(33):25372–25380PubMedCrossRefGoogle Scholar
  132. 132.
    Sun YP, Tjonahen E, Keledjian R, Zhu M, Yang R, Recchiuti A, Pillai PS, Petasis NA, Serhan CN (2009) Anti-inflammatory and pro-resolving properties of benzo-lipoxin A(4) analogs. Prostaglandins Leukot Essent Fatty Acids 81(5–6):357–366PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Clish CB, O’Brien JA, Gronert K, Stahl GL, Petasis NA, Serhan CN (1999) Local and systemic delivery of a stable aspirin-triggered lipoxin prevents neutrophil recruitment in vivo. Proc Natl Acad Sci USA 96(14):8247–8252PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN (1997) Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med 185(9):1693–1704PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Bohr S, Patel SJ, Sarin D, Irimia D, Yarmush ML, Berthiaume F (2012) Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model. Wound Repair Regen 21(1):35–43PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Kim TH, Kim GD, Jin YH, Park YS, Park CS (2012) Omega-3 fatty acid-derived mediator, resolvin E1, ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis in NC/Nga mice. Int Immunopharmacol 14(4):384–391PubMedCrossRefGoogle Scholar
  137. 137.
    Wu SH, Chen XQ, Liu B, Wu HJ, Dong L (2012) Efficacy and safety of 15(R/S)-methyl-lipoxin A(4) in topical treatment of infantile eczema. Br J Dermatol 168(1):172–178CrossRefGoogle Scholar
  138. 138.
    Walker J, Dichter E, Lacorte G, Kerner D, Spur B, Rodriguez A, Yin K (2011) Lipoxin a4 increases survival by decreasing systemic inflammation and bacterial load in sepsis. Shock 36(4):410–416PubMedCrossRefGoogle Scholar
  139. 139.
    Arita M, Yoshida M, Hong S, Tjonahen E, Glickman JN, Petasis NA, Blumberg RS, Serhan CN (2005) Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci USA 102(21):7671–7676PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Bento AF, Claudino RF, Dutra RC, Marcon R, Calixto JB (2011) Omega-3 fatty acid-derived mediators 17(R)-hydroxy docosahexaenoic acid, aspirin-triggered resolvin D1 and resolvin D2 prevent experimental colitis in mice. J Immunol 187(4):1957–1969PubMedCrossRefGoogle Scholar
  141. 141.
    Campbell EL, MacManus CF, Kominsky DJ, Keely S, Glover LE, Bowers BE, Scully M, Bruyninckx WJ, Colgan SP (2010) Resolvin E1-induced intestinal alkaline phosphatase promotes resolution of inflammation through LPS detoxification. Proc Natl Acad Sci USA 107(32):14298–14303PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Aoki H, Hisada T, Ishizuka T, Utsugi M, Kawata T, Shimizu Y, Okajima F, Dobashi K, Mori M (2008) Resolvin E1 dampens airway inflammation and hyperresponsiveness in a murine model of asthma. Biochem Biophys Res Commun 367(2):509–515PubMedCrossRefGoogle Scholar
  143. 143.
    Aoki H, Hisada T, Ishizuka T, Utsugi M, Ono A, Koga Y, Sunaga N, Nakakura T, Okajima F, Dobashi K, Mori M (2010) Protective effect of resolvin E1 on the development of asthmatic airway inflammation. Biochem Biophys Res Commun 400(1):128–133PubMedCrossRefGoogle Scholar
  144. 144.
    Barnig C, Cernadas M, Dutile S, Liu X, Perrella MA, Kazani S, Wechsler ME, Israel E, Levy BD (2013) Lipoxin A4 regulates natural killer cell and type 2 innate lymphoid cell activation in asthma. Sci Transl Med 5(174):174ra126CrossRefGoogle Scholar
  145. 145.
    Christie PE, Spur BW, Lee TH (1992) The effects of lipoxin A4 on airway responses in asthmatic subjects. Am Rev Respir Dis 145(6):1281–1284PubMedCrossRefGoogle Scholar
  146. 146.
    Krishnamoorthy N, Burkett PR, Dalli J, Abdulnour RE, Colas R, Ramon S, Phipps RP, Petasis NA, Kuchroo VK, Serhan CN, Levy BD (2015) Cutting edge: maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation. J Immunol 194(3):863–867PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Levy BD, De Sanctis GT, Devchand PR, Kim E, Ackerman K, Schmidt BA, Szczeklik W, Drazen JM, Serhan CN (2002) Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4). Nat Med 8(9):1018–1023PubMedCrossRefGoogle Scholar
  148. 148.
    Rogerio AP, Haworth O, Croze R, Oh SF, Uddin M, Carlo T, Pfeffer MA, Priluck R, Serhan CN, Levy BD (2012) Resolvin D1 and aspirin-triggered resolvin D1 promote resolution of allergic airways responses. J Immunol 189(4):1983–1991PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Karp CL, Flick LM, Park KW, Softic S, Greer TM, Keledjian R, Yang R, Uddin J, Guggino WB, Atabani SF, Belkaid Y, Xu Y, Whitsett JA, Accurso FJ, Wills-Karp M, Petasis NA (2004) Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway. Nat Immunol 5(4):388–392PubMedCrossRefGoogle Scholar
  150. 150.
    Abdulnour RE, Dalli J, Colby JK, Krishnamoorthy N, Timmons JY, Tan SH, Colas RA, Petasis NA, Serhan CN, Levy BD (2014) Maresin 1 biosynthesis during platelet-neutrophil interactions is organ-protective. Proc Natl Acad Sci USA 111(46):16526–16531PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    El Kebir D, Gjorstrup P, Filep JG (2012) Resolvin E1 promotes phagocytosis-induced neutrophil apoptosis and accelerates resolution of pulmonary inflammation. Proc Natl Acad Sci USA 109(37):14983–14988PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    El Kebir D, Jozsef L, Pan W, Wang L, Petasis NA, Serhan CN, Filep JG (2009) 15-epi-lipoxin A4 inhibits myeloperoxidase signaling and enhances resolution of acute lung injury. Am J Respir Crit Care Med 180(4):311–319PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Tang H, Liu Y, Yan C, Petasis NA, Serhan CN, Gao H (2014) Protective actions of aspirin-triggered (17R) resolvin D1 and its analogue, 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester, in C5a-dependent IgG immune complex-induced inflammation and lung injury. J Immunol 193(7):3769–3778PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Wang B, Gong X, Wan JY, Zhang L, Zhang Z, Li HZ, Min S (2011) Resolvin D1 protects mice from LPS-induced acute lung injury. Pulm Pharmacol Ther 24(4):434–441PubMedCrossRefGoogle Scholar
  155. 155.
    Hasturk H, Kantarci A, Goguet-Surmenian E, Blackwood A, Andry C, Serhan CN, Van Dyke TE (2007) Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol 179(10):7021–7029PubMedCrossRefGoogle Scholar
  156. 156.
    Hasturk H, Kantarci A, Ohira T, Arita M, Ebrahimi N, Chiang N, Petasis NA, Levy BD, Serhan CN, Van Dyke TE (2006) RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis. FASEB J 20(2):401–403PubMedGoogle Scholar
  157. 157.
    Serhan CN, Jain A, Marleau S, Clish C, Kantarci A, Behbehani B, Colgan SP, Stahl GL, Merched A, Petasis NA, Chan L, Van Dyke TE (2003) Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators. J Immunol 171(12):6856–6865PubMedCrossRefGoogle Scholar
  158. 158.
    Connor KM, SanGiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, Hong S, Pravda EA, Majchrzak S, Carper D, Hellstrom A, Kang JX, Chew EY, Salem N, Serhan CN, Smith LEH (2007) Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med 13(7):868–873PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Jin Y, Arita M, Zhang Q, Saban DR, Chauhan SK, Chiang N, Serhan CN, Dana R (2009) Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid mediators. Invest Ophthalmol Vis Sci 50(10):4743–4752PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Li N, He J, Schwartz CE, Gjorstrup P, Bazan HEP (2010) Resolvin E1 improves tear production and decreases inflammation in a dry eye mouse model. J Ocul Pharmacol Ther 26(5):431–439PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Rajasagi NK, Reddy PB, Mulik S, Gjorstrup P, Rouse BT (2013) Neuroprotectin D1 reduces the severity of herpes simplex virus-induced corneal immunopathology. Invest Ophthalmol Vis Sci 54(9):6269–6279PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Rajasagi NK, Reddy PBJ, Suryawanshi A, Mulik S, Gjorstrup P, Rouse BT (2011) Controlling herpes simplex virus-induced ocular inflammatory lesions with the lipid-derived mediator resolvin E1. J Immunol 186(3):1735–1746PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Settimio R, Clara DF, Franca F, Francesca S, Michele D (2012) Resolvin D1 reduces the immunoinflammatory response of the rat eye following uveitis. Mediators Inflamm 2012:318621PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Conte FP, Menezes-de-Lima O Jr, Verri WA Jr, Cunha FQ, Penido C, Henriques MG (2010) Lipoxin A(4) attenuates zymosan-induced arthritis by modulating endothelin-1 and its effects. Br J Pharmacol 161(4):911–924PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Lima-Garcia JF, Dutra RC, da Silva K, Motta EM, Campos MM, Calixto JB (2011) The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats. Br J Pharmacol 164(2):278–293PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Norling LV, Spite M, Yang R, Flower RJ, Perretti M, Serhan CN (2011) Cutting edge: Humanized nano-proresolving medicines mimic inflammation-resolution and enhance wound healing. J Immunol 186(10):5543–5547PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Brancaleone V, Gobbetti T, Cenac N, le Faouder P, Colom B, Flower RJ, Vergnolle N, Nourshargh S, Perretti M (2013) A vasculo-protective circuit centered on lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 operative in murine microcirculation. Blood 122(4):608–617PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Chiang N, Gronert K, Clish CB, O’Brien JA, Freeman MW, Serhan CN (1999) Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion. J Clin Invest 104(3):309–316PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Duffield JS, Hong S, Vaidya VS, Lu Y, Fredman G, Serhan CN, Bonventre JV (2006) Resolvin D series and protectin D1 mitigate acute kidney injury. J Immunol 177(9):5902–5911PubMedCrossRefGoogle Scholar
  170. 170.
    Keyes KT, Ye Y, Lin Y, Zhang C, Perez-Polo JR, Gjorstrup P, Birnbaum Y (2010) Resolvin E1 protects the rat heart against reperfusion injury. Am J Physiol Heart Circ Physiol 299(1):H153–H164PubMedCrossRefGoogle Scholar
  171. 171.
    Gonzalez-Periz A, Horrillo R, Ferre N, Gronert K, Dong B, Moran-Salvador E, Titos E, Martinez-Clemente M, Lopez-Parra M, Arroyo V, Claria J (2009) Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J 23(6):1946–1957PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Hellmann J, Tang Y, Kosuri M, Bhatnagar A, Spite M (2011) Resolvin D1 decreases adipose tissue macrophage accumulation and improves insulin sensitivity in obese-diabetic mice. FASEB J 25(7):2399–2407PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Rius B, Titos E, Moran-Salvador E, Lopez-Vicario C, Garcia-Alonso V, Gonzalez-Periz A, Arroyo V, Claria J (2014) Resolvin D1 primes the resolution process initiated by calorie restriction in obesity-induced steatohepatitis. FASEB J 28(2):836–848PubMedCrossRefGoogle Scholar
  174. 174.
    Tang Y, Zhang MJ, Hellmann J, Kosuri M, Bhatnagar A, Spite M (2013) Proresolution therapy for the treatment of delayed healing of diabetic wounds. Diabetes 62(2):37–41Google Scholar
  175. 175.
    Titos E, Rius B, Gonzalez-Periz A, Lopez-Vicario C, Moran-Salvador E, Martinez-Clemente M, Arroyo V, Claria J (2011) Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype. J Immunol 187(10):5408–5418PubMedCrossRefGoogle Scholar
  176. 176.
    Abdelmoaty S, Wigerblad G, Bas DB, Codeluppi S, Fernandez-Zafra T, el El-Awady S, Moustafa Y, Abdelhamid Ael D, Brodin E, Svensson CI (2013) Spinal actions of lipoxin A4 and 17(R)-resolvin D1 attenuate inflammation-induced mechanical hypersensitivity and spinal TNF release. PLoS One 8(9), e75543PubMedPubMedCentralCrossRefGoogle Scholar
  177. 177.
    Bang S, Yoo S, Yang TJ, Cho H, Hwang SW (2011) 17(R)-resolvin D1 specifically inhibits transient receptor potential ion channel vanilloid 3 leading to peripheral antinociception. Br J Pharmacol 165(3):683–692CrossRefGoogle Scholar
  178. 178.
    Huang L, Wang CF, Serhan CN, Strichartz G (2011) Enduring prevention and transient reduction of postoperative pain by intrathecal resolvin D1. Pain 152(3):557–565PubMedCrossRefGoogle Scholar
  179. 179.
    Park CK, Xu ZZ, Liu T, Lu N, Serhan CN, Ji RR (2011) Resolvin D2 is a potent endogenous inhibitor for transient receptor potential subtype V1/A1, inflammatory pain, and spinal cord synaptic plasticity in mice: distinct roles of resolvin D1, D2, and E1. J Neurosci 31(50):18433–18438PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Quan-Xin F, Fan F, Xiang-Ying F, Shu-Jun L, Shi-Qi W, Zhao-Xu L, Xu-Jie Z, Qing-Chuan Z, Wei W (2012) Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia, phosphorylation of NMDA receptors, and cytokines expression in the thoracic spinal dorsal horn. BMC Gastroenterol 12(1):148PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Svensson CI, Zattoni M, Serhan CN (2007) Lipoxins and aspirin-triggered lipoxin inhibit inflammatory pain processing. J Exp Med 204(2):245–252PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    Xu Z-Z, Zhang L, Liu T, Park JY, Berta T, Yang R, Serhan CN, Ji R-R (2010) Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat Med 16(5):592–597PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Xu ZZ, Berta T, Ji RR (2012) Resolvin E1 inhibits neuropathic pain and spinal cord microglial activation following peripheral nerve injury. J Neuroimmune Pharmacol 8(1):37–41PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Devchand PR, Schmidt BA, Primo VC, Q-y Z, Arnaout MA, Serhan CN, Nikolic B (2005) A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils. FASEB J 19(2):203–210PubMedCrossRefGoogle Scholar
  185. 185.
    Levy BD, Zhang QY, Bonnans C, Primo V, Reilly JJ, Perkins DL, Liang Y, Amin Arnaout M, Nikolic B, Serhan CN (2011) The endogenous pro-resolving mediators lipoxin A4 and resolvin E1 preserve organ function in allograft rejection. Prostaglandins Leukot Essent Fatty Acids 84(1–2):43–50PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    Molina-Berrios A, Campos-Estrada C, Henriquez N, Faundez M, Torres G, Castillo C, Escanilla S, Kemmerling U, Morello A, Lopez-Munoz RA, Maya JD (2013) Protective role of acetylsalicylic acid in experimental trypanosoma cruzi infection: evidence of a 15-epi-lipoxin A(4)-mediated effect. PLoS Negl Trop Dis 7(4), e2173PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Shryock N, McBerry C, Salazar Gonzalez RM, Janes S, Costa FT, Aliberti J (2013) Lipoxin A(4) and 15-epi-lipoxin A(4) protect against experimental cerebral malaria by inhibiting IL-12/IFN-gamma in the brain. PLoS One 8(4), e61882PubMedPubMedCentralCrossRefGoogle Scholar
  188. 188.
    Tobin DM, Roca FJ, Oh SF, McFarland R, Vickery TW, Ray JP, Ko DC, Zou Y, Bang ND, Chau TT, Vary JC, Hawn TR, Dunstan SJ, Farrar JJ, Thwaites GE, King MC, Serhan CN, Ramakrishnan L (2012) Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. Cell 148(3):434–446PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Borgeson E, Docherty NG, Murphy M, Rodgers K, Ryan A, O’Sullivan TP, Guiry PJ, Goldschmeding R, Higgins DF, Godson C (2011) Lipoxin A(4) and benzo-lipoxin A(4) attenuate experimental renal fibrosis. FASEB J 25(9):2967–2979PubMedCrossRefGoogle Scholar
  190. 190.
    Merched AJ, Ko K, Gotlinger KH, Serhan CN, Chan L (2008) Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J 22(10):3595–3606PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Norling LV, Dalli J, Flower RJ, Serhan CN, Perretti M (2012) Resolvin D1 limits polymorphonuclear leukocyte recruitment to inflammatory loci: receptor-dependent actions. Arterioscler Thromb Vasc Biol 32(8):1970–1978PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Green EL (1966) Biology of the laboratory mouse, 2nd edn. Dover Publications, New YorkGoogle Scholar
  193. 193.
    Claria J, Dalli J, Yacoubian S, Gao F, Serhan CN (2012) Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat. J Immunol 189(5):2597–2605PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Fredman G, Ozcan L, Spolitu S, Hellmann J, Spite M, Backs J, Tabas I (2014) Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium-activated kinase pathway. Proc Natl Acad Sci USA 111(40):14530–14535PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O’Leary JJ, Ruan Q, Johnson DS, Chen Y, O’Neill LAJ (2010) Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 11(2):141–147PubMedCrossRefGoogle Scholar
  196. 196.
    Fredman G, Li Y, Dalli J, Chiang N, Serhan CN (2012) Self-limited versus delayed resolution of acute inflammation: temporal regulation of pro-resolving mediators and microRNA. Sci Rep 2:639PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Li Y, Dalli J, Chiang N, Baron RM, Quintana C, Serhan CN (2013) Plasticity of leukocytic exudates in resolving acute inflammation is regulated by microRNA and proresolving mediators. Immunity 39(5):885–898PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Brennan EP, Nolan KA, Borgeson E, Gough OS, McEvoy CM, Docherty NG, Higgins DF, Murphy M, Sadlier DM, Ali-Shah ST, Guiry PJ, Savage DA, Maxwell AP, Martin F, Godson C (2013) Lipoxins attenuate renal fibrosis by inducing let-7c and suppressing TGFbetaR1. J Am Soc Nephrol 24(4):627–637PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Fiore S, Ryeom SW, Weller PF, Serhan CN (1992) Lipoxin recognition sites. Specific binding of labeled lipoxin A4 with human neutrophils. J Biol Chem 267(23):16168–16176PubMedGoogle Scholar
  200. 200.
    Murphy PM, Ozcelik T, Kenney RT, Tiffany HL, McDermott D, Francke U (1992) A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family. J Biol Chem 267(11):7637–7643PubMedGoogle Scholar
  201. 201.
    Fiore S, Maddox JF, Perez HD, Serhan CN (1994) Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. J Exp Med 180(1):253–260PubMedCrossRefGoogle Scholar
  202. 202.
    Ye RD, Boulay F, Wang JM, Dahlgren C, Gerard C, Parmentier M, Serhan CN, Murphy PM (2009) International union of basic and clinical pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol Rev 61(2):119–161PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Romano M, Recchia I, Recchiuti A (2007) Lipoxin receptors. TheScientificWorldJournal 7:1393–1412Google Scholar
  204. 204.
    Chiang N, Takano T, Arita M, Watanabe S, Serhan CN (2003) A novel rat lipoxin A4 receptor that is conserved in structure and function. Br J Pharmacol 139(1):89–98Google Scholar
  205. 205.
    Chiang N, Serhan CN, Dahlen SE, Drazen JM, Hay DW, Rovati GE, Shimizu T, Yomizo T, Brink C (2006) The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in vivo. Pharmacol Rev 58(3):463–487Google Scholar
  206. 206.
    Cooray SN, Gobbetti T, Montero-Melendez T, McArthur S, Thompson D, Clark AJL, Flower RJ, Perretti M (2013) Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2 determines proresolving functional responses. Proc Natl Acad Sci 110(45):18232–18237PubMedPubMedCentralCrossRefGoogle Scholar
  207. 207.
    Devchand PR, Arita M, Hong S, Bannenberg G, Moussignac RL, Gronert K, Serhan CN (2003) Human ALX receptor regulates neutrophil recruitment in transgenic mice: roles in inflammation and host defense. FASEB J 17(6):652–659PubMedCrossRefGoogle Scholar
  208. 208.
    Dufton N, Hannon R, Brancaleone V, Dalli J, Patel HB, Gray M, D’Acquisto F, Buckingham JC, Perretti M, Flower RJ (2010) Anti-inflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation. J Immunol 184(5):2611–2619PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Gobbetti T, Coldewey SM, Chen J, McArthur S, le Faouder P, Cenac N, Flower RJ, Thiemermann C, Perretti M (2014) Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis. Proc Natl Acad Sci USA 111(52):18685–18690Google Scholar
  210. 210.
    Morris T, Stables M, Colville-Nash P, Newson J, Bellingan G, de Souza PM, Gilroy DW (2010) Dichotomy in duration and severity of acute inflammatory responses in humans arising from differentially expressed proresolution pathways. Proc Natl Acad Sci USA 107(19):8842–8847PubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Simiele F, Recchiuti A, Mattoscio D, De Luca A, Cianci E, Franchi S, Gatta V, Parolari A, Werba JP, Camera M, Favaloro B, Romano M (2012) Transcriptional regulation of the human FPR2/ALX gene: evidence of a heritable genetic variant that impairs promoter activity. FASEB J 26(3):1323–1333PubMedCrossRefGoogle Scholar
  212. 212.
    Waechter V, Schmid M, Herova M, Weber A, Gunther V, Marti-Jaun J, Wust S, Rosinger M, Gemperle C, Hersberger M (2012) Characterization of the promoter and the transcriptional regulation of the lipoxin A4 receptor (FPR2/ALX) gene in human monocytes and macrophages. J Immunol 188(4):1856–1867PubMedCrossRefGoogle Scholar
  213. 213.
    Pierdomenico AM, Recchiuti A, Simiele F, Codagnone M, Mari VC, Davi G, Romano M (2014) MicroRNA-181b regulates ALX/FPR2 expression and proresolution signaling in human macrophages. J Biol Chem 290(6):3592–3600Google Scholar
  214. 214.
    Gavins FN, Hughes EL, Buss NA, Holloway PM, Getting SJ, Buckingham JC (2011) Leukocyte recruitment in the brain in sepsis: involvement of the annexin 1-FPR2/ALX anti-inflammatory system. FASEB J 26(12):4977–4989CrossRefGoogle Scholar
  215. 215.
    Lee HN, Surh YJ (2013) Resolvin D1-mediated NOX2 inactivation rescues macrophages undertaking efferocytosis from oxidative stress-induced apoptosis. Biochem Pharmacol 86(6):759–769Google Scholar
  216. 216.
    Dalli J, Kraft BD, Colas RA, Shinohara M, Fredenburgh LE, Hess DR, Chiang N, Welty-Wolf KE, Choi AM, Piantadosi CA, Serhan CN (2015) Proresolving lipid mediator profiles in baboon pneumonia are regulated by inhaled carbon monoxide. Am J Respir Cell Mol Biol 53(3):314–325PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Antonio Recchiuti
    • 1
    • 3
  • Eleonora Cianci
    • 1
    • 2
    • 3
  • Felice Simiele
    • 1
    • 3
  • Mario Romano
    • 1
    • 3
    Email author
  1. 1.Department of Medical, Oral and Biotechnological SciencesG. D’Annunzio University of Chieti-PescaraChietiItaly
  2. 2.Department of Medicine and Aging SciencesG. D’Annunzio University of Chieti-PescaraChietiItaly
  3. 3.Center of Excellence on AgingG. D’Annunzio University of Chieti-PescaraChietiItaly

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