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Open Access 01-07-2016 | Review

Key mechanisms governing resolution of lung inflammation

Authors: C. T. Robb, K. H. Regan, D. A. Dorward, A. G. Rossi

Published in: Seminars in Immunopathology | Issue 4/2016

Abstract

Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered.

Leitch AE, Duffin R, Haslett C, Rossi AG (2008) Relevance of granulocyte apoptosis to resolution of inflammation at the respiratory mucosa. Mucosal Immunol 1:350–363. doi:10.1038/mi.2008.31 PubMedCrossRef

Nathan C (2002) Points of control in inflammation. Nature 420:846–852. doi:10.1038/nature01320 PubMedCrossRef

Nathan C, Ding A (2010) Nonresolving inflammation. Cell 140:871–882. doi:10.1016/j.cell.2010.02.029 PubMedCrossRef

Serhan CN, Brain SD, Buckley CD et al (2007) Resolution of inflammation: state of the art, definitions and terms. FASEB J 21:325–332. doi:10.1096/fj.06-7227rev PubMedPubMedCentralCrossRef

Levy BD, Clish CB, Schmidt B et al (2001) Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2:612–619. doi:10.1038/89759 PubMedCrossRef

Bannenberg GL, Chiang N, Ariel A et al (2005) Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 174:4345–4355PubMedCrossRef

Serhan CN, Chiang N (2008) Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Br J Pharmacol 153:S200–S215. doi:10.1038/sj.bjp.0707489 PubMedCrossRef

Buckley CD, Gilroy DW, Serhan CN (2014) Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 40:315–327. doi:10.1016/j.immuni.2014.02.009 PubMedPubMedCentralCrossRef

Michlewska S, McColl A, Rossi AG et al (2007) Clearance of dying cells and autoimmunity. Autoimmunity 40:267–273. doi:10.1080/08916930701357208 PubMedCrossRef

10.

Poon IKH, Lucas CD, Rossi AG, Ravichandran KS (2014) Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 14:166–180. doi:10.1038/nri3607 PubMedPubMedCentralCrossRef

11.

Motwani MP, Gilroy DW (2015) Macrophage development and polarization in chronic inflammation. Semin Immunol 27:257–266. doi:10.1016/j.smim.2015.07.002 PubMedCrossRef

12.

Persson C, Uller L (2010) Transepithelial exit of leucocytes: inflicting, reflecting or resolving airway inflammation? Thorax 65:1111–1115. doi:10.1136/thx.2009.133363 PubMedCrossRef

13.

Gilroy DW, Lawrence T, Perretti M, Rossi AG (2004) Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov 3:401–416. doi:10.1038/nrd1383 PubMedCrossRef

14.

Duffin R, Leitch AE, Fox S et al (2010) Targeting granulocyte apoptosis: mechanisms, models, and therapies. Immunol Rev 236:28–40. doi:10.1111/j.1600-065X.2010.00922.x PubMedCrossRef

15.

Alessandri AL, Sousa LP, Lucas CD et al (2013) Resolution of inflammation: mechanisms and opportunity for drug development. Pharmacol Ther 139:189–212. doi:10.1016/j.pharmthera.2013.04.006 PubMedCrossRef

16.

Perretti M, Leroy X, Bland EJ, Montero-Melendez T (2015) Resolution pharmacology: opportunities for therapeutic innovation in inflammation. Trends Pharmacol Sci 36:737–755. doi:10.1016/j.tips.2015.07.007 PubMedCrossRef

17.

Sonnenberg GF, Artis D (2015) Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat Med 21:698–708. doi:10.1038/nm.3892 PubMedPubMedCentralCrossRef

18.

Gilroy D, De Maeyer R (2015) New insights into the resolution of inflammation. Semin Immunol 27:161–168. doi:10.1016/j.smim.2015.05.003 PubMedCrossRef

19.

Tak T, Tesselaar K, Pillay J et al (2013) What’s your age again? Determination of human neutrophil half-lives revisited. J Leukoc Biol 94:595–601. doi:10.1189/jlb.1112571 PubMedCrossRef

20.

Borregaard N, Cowland JB (1997) Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 89:3503–3521PubMed

21.

Serhan CN (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol 25:101–137. doi:10.1146/annurev.immunol.25.022106.141647 PubMedCrossRef

22.

Jones HR, Robb CT, Perretti M, Rossi AG (2016) The role of neutrophils in inflammation resolution. Semin Immunol. doi:10.1016/j.smim.2016.03.007 PubMed

23.

Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–57PubMedPubMedCentralCrossRef

24.

Fridlender ZG, Albelda SM (2012) Tumor-associated neutrophils: friend or foe? Carcinogenesis 33:949–955. doi:10.1093/carcin/bgs123 PubMedCrossRef

25.

Kobayashi Y (2015) Neutrophil biology: an update. EXCLI J 14:220–227. doi: 10.17179/excli2015-102

26.

Buckley CD, Ross EA, McGettrick HM et al (2006) Identification of a phenotypically and functionally distinct population of long-lived neutrophils in a model of reverse endothelial migration. J Leukoc Biol 79:303–311. doi:10.1189/jlb.0905496 PubMedCrossRef

27.

Lucas CD, Hoodless LJ, Rossi AG (2014) Swimming against the tide: drugs drive neutrophil reverse migration. Sci Transl Med 6:225fs9. doi:10.1126/scitranslmed.3008666 PubMedCrossRef

28.

Robertson AL, Holmes GR, Bojarczuk AN et al (2014) A zebrafish compound screen reveals modulation of neutrophil reverse migration as an anti-inflammatory mechanism. Sci Transl Med 6:225ra29. doi:10.1126/scitranslmed.3007672 PubMedPubMedCentralCrossRef

29.

Tauzin S, Starnes TW, Becker FB et al (2014) Redox and Src family kinase signaling control leukocyte wound attraction and neutrophil reverse migration. J Cell Biol 207:589–598. doi:10.1083/jcb.201408090 PubMedPubMedCentralCrossRef

30.

Colom B, Bodkin JV, Beyrau M et al (2015) Leukotriene B4-neutrophil elastase axis drives neutrophil reverse transendothelial cell migration in vivo. Immunity 42:1075–1086. doi:10.1016/j.immuni.2015.05.010 PubMedPubMedCentralCrossRef

31.

Ellett F, Elks PM, Robertson AL, et al. (2015) Defining the phenotype of neutrophils following reverse migration in zebrafish. J Leukoc Biol jlb.3MA0315–105R. doi: 10.1189/jlb.3MA0315-105R

32.

Powell DR, Huttenlocher A (2016) Neutrophils in the tumor microenvironment. Trends Immunol 37:41–52. doi:10.1016/j.it.2015.11.008 PubMedCrossRef

33.

Yousefi S, Gold JA, Andina N et al (2008) Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med 14:949–53. doi:10.1038/nm.1855 PubMedCrossRef

34.

Ueki S, Melo RCN, Ghiran I et al (2013) Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans. Blood 121:2074–2083. doi:10.1182/blood-2012-05-432088 PubMedPubMedCentralCrossRef

35.

Stern M, Meagher L, Savill J, Haslett C (1992) Apoptosis in human eosinophils. Programmed cell death in the eosinophil leads to phagocytosis by macrophages and is modulated by IL-5. J Immunol 148:3543–9PubMed

36.

Henderson WR, Jörg A, Klebanoff SJ (1982) Eosinophil peroxidase-mediated inactivation of leukotrienes B4, C4, and D4. J Immunol 128:2609–2613PubMed

37.

Henderson WR, Jong EC, Klebanoff SJ (1980) Binding of eosinophil peroxidase to mast cell granules with retention of peroxidatic activity. J Immunol 124:1383–1388PubMed

38.

Rosenberg HF, Domachowske JB (2001) Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens. J Leukoc Biol 70:691–698PubMed

39.

Drake MG, Bivins-Smith ER, Proskocil BJ et al (2016) Human and mouse eosinophils have antiviral activity against parainfluenza virus. Am J Respir Cell Mol Biol. doi:10.1165/rcmb.2015-0405OC

40.

Felton JM, Lucas CD, Rossi AG, Dransfield I (2014) Eosinophils in the lung—modulating apoptosis and efferocytosis in airway inflammation. Front Immunol. doi:10.3389/fimmu.2014.00302 PubMedPubMedCentral

41.

Falcone FH, Haas H, Gibbs BF (2000) The human basophil: a new appreciation of its role in immune responses. Blood 96:4028–4038PubMed

42.

Gordon S, Plüddemann A, Martinez Estrada F (2014) Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev 262:36–55. doi:10.1111/imr.12223 PubMedPubMedCentralCrossRef

43.

Hussell T, Bell TJ (2014) Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol 14:81–93. doi:10.1038/nri3600 PubMedCrossRef

44.

Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13. doi:10.12703/P6-13 PubMedPubMedCentralCrossRef

45.

Murray PJ, Allen JE, Biswas SK et al (2014) Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41:14–20. doi:10.1016/j.immuni.2014.06.008 PubMedPubMedCentralCrossRef

46.

Savill J (1997) Recognition and phagocytosis of cells undergoing apoptosis. Br Med Bull 53:491–508PubMedCrossRef

47.

Kaur M, Bell T, Salek-Ardakani S, Hussell T (2015) Macrophage adaptation in airway inflammatory resolution. Eur Respir Rev 24:510–515. doi:10.1183/16000617.0030-2015 PubMedCrossRef

48.

Kawkitinarong K, Linz-McGillem L, Birukov KG, Garcia JGN (2004) Differential regulation of human lung epithelial and endothelial barrier function by thrombin. Am J Respir Cell Mol Biol 31:517–527. doi:10.1165/rcmb.2003-0432OC PubMedCrossRef

49.

Crosby LM, Waters CM (2010) Epithelial repair mechanisms in the lung. Am J Physiol Lung Cell Mol Physiol 298:L715–L731. doi:10.1152/ajplung.00361.2009 PubMedPubMedCentralCrossRef

50.

Borish L, Joseph BZ (1992) Inflammation and the allergic response. Med Clin N Am 76:765–787PubMedCrossRef

51.

Amin K (2012) The role of mast cells in allergic inflammation. Respir Med 106:9–14. doi:10.1016/j.rmed.2011.09.007 PubMedCrossRef

52.

Culley FJ (2009) Natural killer cells in infection and inflammation of the lung. Immunology 128:151–163. doi:10.1111/j.1365-2567.2009.03167.x PubMedPubMedCentralCrossRef

53.

Condon TV, Sawyer RT, Fenton MJ, Riches DWH (2011) Lung dendritic cells at the innate-adaptive immune interface. J Leukoc Biol 90:883–895. doi:10.1189/jlb.0311134 PubMedPubMedCentralCrossRef

54.

Fox S, Leitch AE, Duffin R et al (2010) Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease. J Innate Immun 2:216–227. doi:10.1159/000284367 PubMedPubMedCentralCrossRef

55.

Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316PubMedCrossRef

56.

Earnshaw WC, Martins LM, Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68:383–424. doi:10.1146/annurev.biochem.68.1.383 PubMedCrossRef

57.

Maianski NA, Roos D, Kuijpers TW (2003) Tumor necrosis factor alpha induces a caspase-independent death pathway in human neutrophils. Blood 101:1987–1995. doi:10.1182/blood-2002-02-0522 PubMedCrossRef

58.

Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491–501PubMedCrossRef

59.

Schug ZT, Gonzalvez F, Houtkooper RH et al (2011) BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death Differ 18:538–548. doi:10.1038/cdd.2010.135 PubMedCrossRef

60.

Arandjelovic S, Ravichandran KS (2015) Phagocytosis of apoptotic cells in homeostasis. Nat Immunol 16:907–917. doi:10.1038/ni.3253 PubMedPubMedCentralCrossRef

61.

Truman LA, Ford CA, Pasikowska M et al (2008) CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis. Blood 112:5026–5036. doi:10.1182/blood-2008-06-162404 PubMedCrossRef

62.

Lauber K, Bohn E, Kröber SM et al (2003) Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113:717–730PubMedCrossRef

63.

Gude DR, Alvarez SE, Paugh SW et al (2008) Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a “come-and-get-me” signal. FASEB J 22:2629–2638. doi:10.1096/fj.08-107169 PubMedPubMedCentralCrossRef

64.

Elliott MR, Chekeni FB, Trampont PC et al (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461:282–286. doi:10.1038/nature08296 PubMedPubMedCentralCrossRef

65.

Gardai SJ, Bratton DL, Ogden CA, Henson PM (2006) Recognition ligands on apoptotic cells: a perspective. J Leukoc Biol 79:896–903. doi:10.1189/jlb.1005550 PubMedCrossRef

66.

Fadok VA, Voelker DR, Campbell PA et al (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148:2207–2216PubMed

67.

Fadok VA, Bratton DL, Rose DM et al (2000) A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85–90. doi:10.1038/35011084 PubMedCrossRef

68.

Hochreiter-Hufford A, Ravichandran KS (2013) Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb Perspe ct Biol 5:a008748. doi:10.1101/cshperspect.a008748 CrossRef

69.

Serhan CN, Chiang N, Dalli J, Levy BD (2014) Lipid mediators in the resolution of inflammation. Cold Spring Harb Perspect Biol a016311. doi: 10.1101/cshperspect.a016311

70.

Cavassani KA, Ishii M, Wen H et al (2008) TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. J Exp Med 205:2609–2621. doi:10.1084/jem.20081370 PubMedPubMedCentralCrossRef

71.

Zitvogel L, Kepp O, Kroemer G (2010) Decoding cell death signals in inflammation and immunity. Cell 140:798–804. doi:10.1016/j.cell.2010.02.015 PubMedCrossRef

72.

Kono H, Rock KL (2008) How dying cells alert the immune system to danger. Nat Rev Immunol 8:279–289. doi:10.1038/nri2215 PubMedPubMedCentralCrossRef

73.

Brinkmann V, Reichard U, Goosmann C et al (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–5PubMedCrossRef

74.

Yousefi S, Mihalache C, Kozlowski E et al (2009) Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ 16:1438–44. doi:10.1038/cdd.2009.96 PubMedCrossRef

75.

Pilsczek FH, Salina D, Poon KKH et al (2010) A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol 185:7413–7425. doi:10.4049/jimmunol.1000675 PubMedCrossRef

76.

Fuchs TA, Abed U, Goosmann C et al (2007) Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 176:231–41PubMedPubMedCentralCrossRef

77.

Urban CF, Ermert D, Schmid M et al (2009) Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog 5:e1000639. doi:10.1371/journal.ppat.1000639 PubMedPubMedCentralCrossRef

78.

Neeli I, Radic M (2012) Knotting the NETs: analyzing histone modifications in neutrophil extracellular traps. Arthritis Res Ther 14:115. doi:10.1186/ar3773 PubMedPubMedCentralCrossRef

79.

Neeli I, Dwivedi N, Khan S, Radic M (2009) Regulation of extracellular chromatin release from neutrophils. J Innate Immun 1:194–201. doi:10.1159/000206974 PubMedCrossRef

80.

Gray RD, Lucas CD, Mackellar A et al (2013) Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps. J Inflamm (Lond) 10:12. doi:10.1186/1476-9255-10-12 CrossRef

81.

Saitoh T, Komano J, Saitoh Y et al (2012) Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe 12:109–116. doi:10.1016/j.chom.2012.05.015 PubMedCrossRef

82.

Urban CF, Reichard U, Brinkmann V, Zychlinsky A (2006) Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol 8:668–76PubMedCrossRef

83.

Abi Abdallah DS, Lin C, Ball CJ et al (2012) Toxoplasma gondii triggers release of human and mouse neutrophil extracellular traps. Infect Immun 80:768–777. doi:10.1128/IAI.05730-11 PubMedPubMedCentralCrossRef

84.

Wartha F, Beiter K, Albiger B et al (2007) Capsule and D-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular traps. Cell Microbiol 9:1162–1171. doi:10.1111/j.1462-5822.2006.00857.x PubMedCrossRef

85.

Buchanan JT, Simpson AJ, Aziz RK et al (2006) DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps. Curr Biol 16:396–400. doi:10.1016/j.cub.2005.12.039 PubMedCrossRef

86.

Steinberg BE, Grinstein S (2007) Unconventional roles of the NADPH oxidase: signaling, ion homeostasis, and cell death. Sci STKE 2007:pe11. doi:10.1126/stke.3792007pe11 PubMedCrossRef

87.

Wartha F, Henriques-Normark B (2008) ETosis: a novel cell death pathway. Sci Signal 1:pe25. doi:10.1126/stke.121pe25 PubMedCrossRef

88.

Robb CT, Dyrynda EA, Gray RD et al (2014) Invertebrate extracellular phagocyte traps show that chromatin is an ancient defence weapon. Nat Commun 5:4627. doi:10.1038/ncomms5627 PubMedPubMedCentralCrossRef

89.

Kasama T, Miwa Y, Isozaki T et al (2005) Neutrophil-derived cytokines: potential therapeutic targets in inflammation. Curr Drug Targets Inflamm Allergy 4:273–279PubMedCrossRef

90.

Zawrotniak M, Rapala-Kozik M (2013) Neutrophil extracellular traps (NETs)—formation and implications. Acta Biochim Pol 60:277–284PubMed

91.

Bosmann M, Grailer JJ, Ruemmler R et al (2013) Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury. FASEB J 27:5010–5021. doi:10.1096/fj.13-236380 PubMedPubMedCentralCrossRef

92.

Caudrillier A, Kessenbrock K, Gilliss BM et al (2012) Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest 122:2661–2671. doi:10.1172/JCI61303 PubMedPubMedCentralCrossRef

93.

Narasaraju T, Yang E, Samy RP et al (2011) Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol 179:199–210. doi:10.1016/j.ajpath.2011.03.013 PubMedPubMedCentralCrossRef

94.

Manzenreiter R, Kienberger F, Marcos V et al (2012) Ultrastructural characterization of cystic fibrosis sputum using atomic force and scanning electron microscopy. J Cyst Fibros 11:84–92. doi:10.1016/j.jcf.2011.09.008 PubMedCrossRef

95.

Dwyer M, Shan Q, Ortona SD et al (2014) Cystic fibrosis sputum DNA has NETosis characteristics and neutrophil extracellular trap release is regulated by macrophage migration-inhibitory factor. J Innate Immun 6:765–779. doi:10.1159/000363242 PubMedPubMedCentralCrossRef

96.

Fuxman Bass JI, Russo DM, Gabelloni ML et al (2010) Extracellular DNA: a major proinflammatory component of Pseudomonas aeruginosa biofilms. J Immunol 184:6386–6395. doi:10.4049/jimmunol.0901640 PubMedCrossRef

97.

Young RL, Malcolm KC, Kret JE et al (2011) Neutrophil extracellular trap (NET)-mediated killing of Pseudomonas aeruginosa: evidence of acquired resistance within the CF airway, independent of CFTR. PLoS One 6:e23637. doi:10.1371/journal.pone.0023637 PubMedPubMedCentralCrossRef

98.

Dworski R, Simon H-U, Hoskins A, Yousefi S (2011) Eosinophil and neutrophil extracellular DNA traps in human allergic asthmatic airways. J Allergy Clin Immunol 127:1260–1266. doi:10.1016/j.jaci.2010.12.1103 PubMedPubMedCentralCrossRef

99.

Grabcanovic-Musija F, Obermayer A, Stoiber W et al (2015) Neutrophil extracellular trap (NET) formation characterises stable and exacerbated COPD and correlates with airflow limitation. Respir Res. doi:10.1186/s12931-015-0221-7 PubMedPubMedCentral

100.

Pedersen F, Marwitz S, Holz O et al (2015) Neutrophil extracellular trap formation and extracellular DNA in sputum of stable COPD patients. Respir Med 109:1360–1362. doi:10.1016/j.rmed.2015.08.008 PubMedCrossRef

101.

Ramos-Kichik V, Mondragón-Flores R, Mondragón-Castelán M et al (2009) Neutrophil extracellular traps are induced by Mycobacterium tuberculosis. Tuberculosis (Edinb) 89:29–37. doi:10.1016/j.tube.2008.09.009 CrossRef

102.

Cheng OZ, Palaniyar N (2013) NET balancing: a problem in inflammatory lung diseases. Front Immunol. doi:10.3389/fimmu.2013.00001

103.

Röhm M, Grimm MJ, Auria ACD et al (2014) NADPH oxidase promotes neutrophil extracellular trap formation in pulmonary aspergillosis. Infect Immun 82:1766–1777. doi:10.1128/IAI.00096-14 PubMedPubMedCentralCrossRef

104.

Coxon A, Rieu P, Barkalow FJ et al (1996) A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation. Immunity 5:653–666PubMedCrossRef

105.

Romani L, Fallarino F, De Luca A et al (2008) Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature 451:211–215. doi:10.1038/nature06471 PubMedCrossRef

106.

Ryter SW, Choi AMK (2015) Autophagy in lung disease pathogenesis and therapeutics. Redox Biol 4:215–225. doi:10.1016/j.redox.2014.12.010 PubMedPubMedCentralCrossRef

107.

Ponpuak M, Davis AS, Roberts EA et al (2010) Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties. Immunity 32:329–341. doi:10.1016/j.immuni.2010.02.009 PubMedPubMedCentralCrossRef

108.

Zhang R, Chi X, Wang S et al (2014) The regulation of autophagy by influenza A virus, the regulation of autophagy by influenza A virus. BioMed Res Int 2014:498083. doi:10.1155/2014/498083 PubMedPubMedCentral

109.

Lam HC, Cloonan SM, Bhashyam AR et al (2013) Histone deacetylase 6-mediated selective autophagy regulates COPD-associated cilia dysfunction. J Clin Invest 123:5212–5230. doi:10.1172/JCI69636 PubMedPubMedCentralCrossRef

110.

Qing DY, Conegliano D, Shashaty MGS et al (2014) Red blood cells induce necroptosis of lung endothelial cells and increase susceptibility to lung inflammation. Am J Respir Crit Care Med 190:1243–1254. doi:10.1164/rccm.201406-1095OC PubMedPubMedCentralCrossRef

111.

Kitur K, Parker D, Nieto P et al (2015) Toxin-induced necroptosis is a major mechanism of Staphylococcus aureus lung damage. PLoS Pathog 11:e1004820. doi:10.1371/journal.ppat.1004820 PubMedPubMedCentralCrossRef

112.

Pouwels SD, Zijlstra GJ, van der Toorn M, et al. (2015) Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice. Am J Physiol Lung Cell Mol Physiol ajplung.00174.2015. doi: 10.1152/ajplung.00174.2015

113.

Parnaik R, Raff MC, Scholes J (2000) Differences between the clearance of apoptotic cells by professional and non-professional phagocytes. Curr Biol 10:857–860PubMedCrossRef

114.

Wood W, Turmaine M, Weber R et al (2000) Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos. Development 127:5245–5252PubMed

115.

Blume KE, Soeroes S, Keppeler H et al (2012) Cleavage of annexin A1 by ADAM10 during secondary necrosis generates a monocytic “find-me” signal. J Immunol 188:135–145. doi:10.4049/jimmunol.1004073 PubMedCrossRef

116.

Arur S, Uche UE, Rezaul K et al (2003) Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev Cell 4:587–598PubMedCrossRef

117.

Bournazou I, Pound JD, Duffin R et al (2009) Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin. J Clin Invest 119:20–32. doi:10.1172/JCI36226 PubMed

118.

Bournazou I, Mackenzie KJ, Duffin R et al (2010) Inhibition of eosinophil migration by lactoferrin. Immunol Cell Biol 88:220–223. doi:10.1038/icb.2009.86 PubMedCrossRef

119.

Park D, Tosello-Trampont A-C, Elliott MR et al (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430–434. doi:10.1038/nature06329 PubMedCrossRef

120.

Park S-Y, Jung M-Y, Kim H-J et al (2008) Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ 15:192–201. doi:10.1038/sj.cdd.4402242 PubMedCrossRef

121.

Kobayashi N, Karisola P, Peña-Cruz V et al (2007) TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity 27:927–940. doi:10.1016/j.immuni.2007.11.011 PubMedPubMedCentralCrossRef

122.

Nakayama M, Akiba H, Takeda K et al (2009) Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation. Blood 113:3821–3830. doi:10.1182/blood-2008-10-185884 PubMedCrossRef

123.

Lee S-J, So I-S, Park S-Y, Kim I-S (2008) Thymosin beta4 is involved in stabilin-2-mediated apoptotic cell engulfment. FEBS Lett 582:2161–2166. doi:10.1016/j.febslet.2008.03.058 PubMedCrossRef

124.

Park S-Y, Kang K-B, Thapa N et al (2008) Requirement of adaptor protein GULP during stabilin-2-mediated cell corpse engulfment. J Biol Chem 283:10593–10600. doi:10.1074/jbc.M709105200 PubMedCrossRef

125.

Toda S, Hanayama R, Nagata S (2012) Two-step engulfment of apoptotic cells. Mol Cell Biol 32:118–125. doi:10.1128/MCB.05993-11 PubMedPubMedCentralCrossRef

126.

Hanayama R, Tanaka M, Miwa K et al (2002) Identification of a factor that links apoptotic cells to phagocytes. Nature 417:182–187. doi:10.1038/417182a PubMedCrossRef

127.

Anderson HA, Maylock CA, Williams JA et al (2003) Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol 4:87–91. doi:10.1038/ni871 PubMedCrossRef

128.

Ishimoto Y, Ohashi K, Mizuno K, Nakano T (2000) Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J Biochem 127:411–417PubMedCrossRef

129.

Gardai SJ, McPhillips KA, Frasch SC et al (2005) Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 123:321–334. doi:10.1016/j.cell.2005.08.032 PubMedCrossRef

130.

Obeid M, Tesniere A, Ghiringhelli F et al (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61. doi:10.1038/nm1523 PubMedCrossRef

131.

Liu Y, Cousin JM, Hughes J et al (1999) Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes. J Immunol 162:3639–3646PubMed

132.

Giles KM, Ross K, Rossi AG et al (2001) Glucocorticoid augmentation of macrophage capacity for phagocytosis of apoptotic cells is associated with reduced p130Cas expression, loss of paxillin/pyk2 phosphorylation, and high levels of active Rac. J Immunol 167:976–986PubMedCrossRef

133.

McColl A, Bournazos S, Franz S et al (2009) Glucocorticoids induce protein S-dependent phagocytosis of apoptotic neutrophils by human macrophages. J Immunol 183:2167–2175. doi:10.4049/jimmunol.0803503 PubMedCrossRef

134.

Scott RS, McMahon EJ, Pop SM et al (2001) Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411:207–211. doi:10.1038/35075603 PubMedCrossRef

135.

Choi J-Y, Park H-J, Lee Y-J et al (2013) Upregulation of Mer receptor tyrosine kinase signaling attenuated lipopolysaccharide-induced lung inflammation. J Pharmacol Exp Ther 344:447–458. doi:10.1124/jpet.112.199778 PubMedCrossRef

136.

Thorp E, Vaisar T, Subramanian M et al (2011) Shedding of the Mer tyrosine kinase receptor is mediated by ADAM17 protein through a pathway involving reactive oxygen species, protein kinase Cδ, and p38 mitogen-activated protein kinase (MAPK). J Biol Chem 286:33335–33344. doi:10.1074/jbc.M111.263020 PubMedPubMedCentralCrossRef

137.

Lee Y-J, Lee S-H, Youn Y-S et al (2012) Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice. Toxicol Appl Pharmacol 263:61–72. doi:10.1016/j.taap.2012.05.024 PubMedCrossRef

138.

Marwick JA, Dorward DA, Lucas CD et al (2013) Oxygen levels determine the ability of glucocorticoids to influence neutrophil survival in inflammatory environments. J Leukoc Biol 94:1285–1292. doi:10.1189/jlb.0912462 PubMedPubMedCentralCrossRef

139.

Perretti M, Acquisto FD (2009) Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol 9:62–70. doi:10.1038/nri2470 PubMedCrossRef

140.

Perretti M, Chiang N, La M et al (2002) Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nat Med 8:1296–1302. doi:10.1038/nm786 PubMedPubMedCentralCrossRef

141.

Perretti M, Christian H, Wheller SK et al (2000) Annexin I is stored within gelatinase granules of human neutrophil and mobilized on the cell surface upon adhesion but not phagocytosis. Cell Biol Int 24:163–174. doi:10.1006/cbir.1999.0468 PubMedCrossRef

142.

Maderna P, Yona S, Perretti M, Godson C (2005) Modulation of phagocytosis of apoptotic neutrophils by supernatant from dexamethasone-treated macrophages and annexin-derived peptide Ac2–26. J Immunol 174:3727–3733. doi:10.4049/jimmunol.174.6.3727 PubMedCrossRef

143.

Scannell M, Flanagan MB, deStefani A et al (2007) Annexin-1 and peptide derivatives are released by apoptotic cells and stimulate phagocytosis of apoptotic neutrophils by macrophages. J Immunol 178:4595–4605PubMedCrossRef

144.

Goulding NJ, Godolphin JL, Sharland PR et al (1990) Anti-inflammatory lipocortin 1 production by peripheral blood leucocytes in response to hydrocortisone. Lancet 335:1416–1418PubMedCrossRef

145.

Mulla A, LeRoux C, Solito E, Buckingham JC (2005) Correlation between the antiinflammatory protein annexin 1 (lipocortin 1) and serum cortisol in subjects with normal and dysregulated adrenal function. J Clin Endocrinol Metab 90:557–562. doi:10.1210/jc.2004-1230 PubMedCrossRef

146.

Vago JP, Nogueira CRC, Tavares LP et al (2012) Annexin A1 modulates natural and glucocorticoid-induced resolution of inflammation by enhancing neutrophil apoptosis. J Leukoc Biol 92:249–258. doi:10.1189/jlb.0112008 PubMedCrossRef

147.

Morimoto K, Janssen WJ, Fessler MB et al (2006) Lovastatin enhances clearance of apoptotic cells (efferocytosis) with implications for chronic obstructive pulmonary disease. J Immunol 176:7657–7665PubMedCrossRef

148.

Yun JH, Henson PM, Tuder RM (2008) Phagocytic clearance of apoptotic cells: role in lung disease. Expert Rev Respir Med 2:753–765. doi:10.1586/17476348.2.6.753 PubMedPubMedCentralCrossRef

149.

Grabiec AM, Hussell T (2016) The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation. Semin Immunopathol. doi:10.1007/s00281-016-0555-3 PubMedCentral

150.

Dockrell DH, Marriott HM, Prince LR et al (2003) Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infection. J Immunol 171:5380–5388PubMedCrossRef

151.

Aberdein JD, Cole J, Bewley MA et al (2013) Alveolar macrophages in pulmonary host defence the unrecognized role of apoptosis as a mechanism of intracellular bacterial killing. Clin Exp Immunol 174:193–202. doi:10.1111/cei.12170 PubMedPubMedCentral

152.

Curtis JL, Todt JC, Hu B et al (2009) Tyro3 receptor tyrosine kinases in the heterogeneity of apoptotic cell uptake. Front Biosci (Landmark Ed) 14:2631–2646CrossRef

153.

Janssen WJ, McPhillips KA, Dickinson MG et al (2008) Surfactant proteins A and D suppress alveolar macrophage phagocytosis via interaction with SIRP alpha. Am J Respir Crit Care Med 178:158–167. doi:10.1164/rccm.200711-1661OC PubMedPubMedCentralCrossRef

154.

McCubbrey AL, Curtis JL (2013) Efferocytosis and lung disease. Chest 143:1750–1757. doi:10.1378/chest.12-2413 PubMedPubMedCentralCrossRef

155.

Xiong Z, Leme AS, Ray P et al (2011) CX3CR1+ lung mononuclear phagocytes spatially confined to the interstitium produce TNF-α and IL-6 and promote cigarette smoke-induced emphysema. J Immunol 186:3206–3214. doi:10.4049/jimmunol.1003221 PubMedPubMedCentralCrossRef

156.

Desch AN, Randolph GJ, Murphy K et al (2011) CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic cell-associated antigen. J Exp Med 208:1789–1797. doi:10.1084/jem.20110538 PubMedPubMedCentralCrossRef

157.

Walsh GM, Sexton DW, Blaylock MG, Convery CM (1999) Resting and cytokine-stimulated human small airway epithelial cells recognize and engulf apoptotic eosinophils. Blood 94:2827–2835PubMed

158.

Sexton DW, Blaylock MG, Walsh GM (2001) Human alveolar epithelial cells engulf apoptotic eosinophils by means of integrin- and phosphatidylserine receptor-dependent mechanisms: a process upregulated by dexamethasone. J Allergy Clin Immunol 108:962–969. doi:10.1067/mai.2001.119414 PubMedCrossRef

159.

Juncadella IJ, Kadl A, Sharma AK et al (2013) Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature 493:547–551. doi:10.1038/nature11714 PubMedCrossRef

160.

Samuelsson B, Dahlén SE, Lindgren JA et al (1987) Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237:1171–1176PubMedCrossRef

161.

Levy BD, Serhan CN (2014) Resolution of acute inflammation in the lung. Annu Rev Physiol 76:467–492. doi:10.1146/annurev-physiol-021113-170408 PubMedCrossRef

162.

Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8:349–361. doi:10.1038/nri2294 PubMedPubMedCentralCrossRef

163.

Serhan CN (2014) Pro-resolving lipid mediators are leads for resolution physiology. Nature 510:92–101. doi:10.1038/nature13479 PubMedPubMedCentralCrossRef

164.

Gilroy DW, Colville-Nash PR, Willis D et al (1999) Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med 5:698–701. doi:10.1038/9550 PubMedCrossRef

165.

Fukunaga K, Kohli P, Bonnans C et al (2005) Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury. J Immunol 174:5033–5039PubMedCrossRef

166.

Schwab JM, Chiang N, Arita M, Serhan CN (2007) Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447:869–874. doi:10.1038/nature05877 PubMedPubMedCentralCrossRef

167.

Ye RD, Boulay F, Wang JM et al (2009) International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol Rev 61:119–161. doi:10.1124/pr.109.001578 PubMedPubMedCentralCrossRef

168.

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 U S A 81:5335–5339PubMedPubMedCentralCrossRef

169.

Serhan CN, Sheppard KA (1990) Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro. J Clin Invest 85:772–780. doi:10.1172/JCI114503 PubMedPubMedCentralCrossRef

170.

Levy BD, Romano M, Chapman HA et al (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 92:1572–1579. doi:10.1172/JCI116738 PubMedPubMedCentralCrossRef

171.

Chiang N, Serhan CN, Dahlén S-E et al (2006) The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in vivo. Pharmacol Rev 58:463–487. doi:10.1124/pr.58.3.4 PubMedCrossRef

172.

Krishnamoorthy S, Recchiuti A, Chiang N et al (2012) Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs. Am J Pathol 180:2018–2027. doi:10.1016/j.ajpath.2012.01.028 PubMedPubMedCentralCrossRef

173.

Krishnamoorthy S, Recchiuti A, Chiang N et al (2010) Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci U S A 107:1660–1665. doi:10.1073/pnas.0907342107 PubMedPubMedCentralCrossRef

174.

Norling LV, Dalli J, Flower RJ et al (2012) Resolvin D1 limits polymorphonuclear leukocyte recruitment to inflammatory loci: receptor-dependent actions. Arterioscler Thromb Vasc Biol 32:1970–1978. doi:10.1161/ATVBAHA.112.249508 PubMedPubMedCentralCrossRef

175.

Arita M, Ohira T, Sun Y-P et al (2007) Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J Immunol 178:3912–3917PubMedCrossRef

176.

Serhan CN, Gotlinger K, Hong S et al (2006) Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol 176:1848–1859PubMedCrossRef

177.

Marcheselli VL, Hong S, Lukiw WJ et al (2003) Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 278:43807–43817. doi:10.1074/jbc.M305841200 PubMedCrossRef

178.

Serhan CN, Yang R, Martinod K et al (2009) Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 206:15–23. doi:10.1084/jem.20081880 PubMedPubMedCentralCrossRef

179.

Dalli J, Zhu M, Vlasenko NA et al (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 27:2573–2583. doi:10.1096/fj.13-227728 PubMedPubMedCentralCrossRef

180.

Serhan CN, Dalli J, Karamnov S et al (2012) Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. FASEB J 26:1755–1765. doi:10.1096/fj.11-201442 PubMedPubMedCentralCrossRef

181.

Levy BD, Bonnans C, Silverman ES et al (2005) Diminished lipoxin biosynthesis in severe asthma. Am J Respir Crit Care Med 172:824–830. doi:10.1164/rccm.200410-1413OC PubMedPubMedCentralCrossRef

182.

Karp CL, Flick LM, Park KW et al (2004) Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway. Nat Immunol 5:388–392. doi:10.1038/ni1056 PubMedCrossRef

183.

Sanak M, Levy BD, Clish CB et al (2000) Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant asthmatics. Eur Respir J 16:44–49PubMedCrossRef

184.

Kowal-Bielecka O, Kowal K, Distler O et al (2005) Cyclooxygenase- and lipoxygenase-derived eicosanoids in bronchoalveolar lavage fluid from patients with scleroderma lung disease: an imbalance between proinflammatory and antiinflammatory lipid mediators. Arthritis Rheum 52:3783–3791. doi:10.1002/art.21432 PubMedCrossRef

185.

Levy BD, Vachier I, Serhan CN (2012) Resolution of inflammation in asthma. Clin Chest Med 33:559–570. doi:10.1016/j.ccm.2012.06.006 PubMedPubMedCentralCrossRef

186.

Freedman SD, Blanco PG, Zaman MM et al (2004) Association of cystic fibrosis with abnormalities in fatty acid metabolism. N Engl J Med 350:560–569. doi:10.1056/NEJMoa021218 PubMedCrossRef

187.

Haworth O, Cernadas M, Levy BD (2011) NK cells are effectors for resolvin E1 in the timely resolution of allergic airway inflammation. J Immunol 186:6129–6135. doi:10.4049/jimmunol.1004007 PubMedCrossRef

188.

Rogerio AP, Haworth O, Croze R et al (2012) Resolvin D1 and aspirin-triggered resolvin D1 promote resolution of allergic airways responses. J Immunol 189:1983–1991. doi:10.4049/jimmunol.1101665 PubMedPubMedCentralCrossRef

189.

Haworth O, Cernadas M, Yang R et al (2008) Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat Immunol 9:873–879. doi:10.1038/ni.1627 PubMedPubMedCentralCrossRef

190.

Winkler J, Orr S, Dalli J et al (2015) Resolvin D4 potent antiiinflammatory proresolving actions confirmed via total synthesis. FASEB J 29:285.10

191.

Winkler JW, Orr SK, Dalli J et al (2016) Resolvin D4 stereoassignment and its novel actions in host protection and bacterial clearance. Sci Rep 6:18972. doi:10.1038/srep18972 PubMedPubMedCentralCrossRef

192.

Levy BD, Kohli P, Gotlinger K et al (2007) Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J Immunol 178:496–502PubMedPubMedCentralCrossRef

193.

Freire MO (2000) Van Dyke TE (2013) Natural resolution of inflammation. Periodontol 63:149–164. doi:10.1111/prd.12034 CrossRef

194.

Basil MC, Levy BD (2016) Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nat Rev Immunol 16:51–67. doi:10.1038/nri.2015.4 PubMedCrossRef

195.

Kolaczkowska E, Kubes P (2013) Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol 13:159–175. doi:10.1038/nri3399 PubMedCrossRef

196.

José R, Williams A, Sulikowski M et al (2015) Regulation of neutrophilic inflammation in lung injury induced by community-acquired pneumonia. Lancet 385(Suppl 1):S52. doi:10.1016/S0140-6736(15)60367-1 PubMedCrossRef

197.

Akinosoglou K, Alexopoulos D (2014) Use of antiplatelet agents in sepsis: a glimpse into the future. Thromb Res 133:131–138. doi:10.1016/j.thromres.2013.07.002 PubMedCrossRef

198.

de Boer JD, Kager LM, Roelofs JJTH et al (2014) Overexpression of activated protein C hampers bacterial dissemination during pneumococcal pneumonia. BMC Infect Dis 14:559. doi:10.1186/s12879-014-0559-3 PubMedPubMedCentralCrossRef

199.

Arnold FW, Bordon J, Fernandez-Botran R et al (2015) Macrolide use and neutrophil function/cytokine levels in hospitalized patients with community-acquired pneumonia: a pilot study. Lung. doi:10.1007/s00408-015-9822-7 PubMed

200.

Mandal P, Chalmers JD, Graham C et al (2014) Atorvastatin as a stable treatment in bronchiectasis: a randomised controlled trial. Lancet Respir Med 2:455–463. doi:10.1016/S2213-2600(14)70050-5 PubMedCrossRef

201.

Troeman DPR, Postma DF, van Werkhoven CH, Oosterheert JJ (2013) The immunomodulatory effects of statins in community-acquired pneumonia: a systematic review. J Infect 67:93–101. doi:10.1016/j.jinf.2013.04.015 PubMedCrossRef

202.

Moret I, Lorenzo MJ, Sarria B et al (2011) Increased lung neutrophil apoptosis and inflammation resolution in nonresponding pneumonia. Eur Respir J 38:1158–1164. doi:10.1183/09031936.00190410 PubMedCrossRef

203.

Rossi AG, Sawatzky DA, Walker A et al (2006) Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med 12:1056–1064. doi:10.1038/nm1468 PubMedCrossRef

204.

Hoogendijk AJ, Roelofs JJTH, Duitman J et al (2012) R-roscovitine reduces lung inflammation induced by lipoteichoic acid and Streptococcus pneumoniae. Mol Med 18:1086–1095. doi:10.2119/molmed.2012.00033 PubMedPubMedCentralCrossRef

205.

Lucas CD, Dorward DA, Tait MA et al (2014) Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung. Mucosal Immunol 7:857–868. doi:10.1038/mi.2013.102 PubMed

206.

Castro CY (2006) ARDS and diffuse alveolar damage: a pathologist’s perspective. Semin Thorac Cardiovasc Surg 18:13–19. doi:10.1053/j.semtcvs.2006.02.001 PubMedCrossRef

207.

Piantadosi CA, Schwartz DA (2004) The acute respiratory distress syndrome. Ann Intern Med 141:460–470PubMedCrossRef

208.

Estenssoro E, Dubin A, Laffaire E et al (2002) Incidence, clinical course, and outcome in 217 patients with acute respiratory distress syndrome. Crit Care Med 30:2450–2456. doi:10.1097/01.CCM.0000034692.46267.02 PubMedCrossRef

209.

Steinberg KP, Milberg JA, Martin TR et al (1994) Evolution of bronchoalveolar cell populations in the adult respiratory distress syndrome. Am J Respir Crit Care Med 150:113–122. doi:10.1164/ajrccm.150.1.8025736 PubMedCrossRef

210.

Headley AS, Tolley E, Meduri GU (1997) Infections and the inflammatory response in acute respiratory distress syndrome. Chest 111:1306–1321PubMedCrossRef

211.

Steinberg KP, Hudson LD, Goodman RB et al (2006) Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 354:1671–1684. doi:10.1056/NEJMoa051693 PubMedCrossRef

212.

Meduri GU, Marik PE, Chrousos GP et al (2008) Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature. Intensive Care Med 34:61–69. doi:10.1007/s00134-007-0933-3 PubMedCrossRef

213.

Peter JV, John P, Graham PL et al (2008) Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ 336:1006–1009. doi:10.1136/bmj.39537.939039.BE PubMedPubMedCentralCrossRef

214.

Tang BMP, Craig JC, Eslick GD et al (2009) Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med 37:1594–1603. doi:10.1097/CCM.0b013e31819fb507 PubMedCrossRef

215.

Kawashima M, Yatsunami J, Fukuno Y et al (2014) Inhibitory effects of 14-membered ring macrolide antibiotics on bleomycin-induced acute lung injury. Lung 180:73–89. doi:10.1007/PL00021246 CrossRef

216.

Leiva M, Ruiz-Bravo A, Jimenez-Valera M (2008) Effects of telithromycin in in vitro and in vivo models of lipopolysaccharide-induced airway inflammation. Chest 134:20–29. doi:10.1378/chest.07-3056 PubMedCrossRef

217.

Noto MJ, Wheeler AP (2012) Macrolides for acute lung injury. Chest 141:1131–1132. doi:10.1378/chest.11-3245 PubMedPubMedCentralCrossRef

218.

Walkey AJ, Wiener RS (2012) Macrolide antibiotics and survival in patients with acute lung injury. Chest 141:1153–1159. doi:10.1378/chest.11-1908 PubMedCrossRef

219.

Bernard GR, Wheeler AP, Russell JA et al (1997) The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med 336:912–918. doi:10.1056/NEJM199703273361303 PubMedCrossRef

220.

Heijerman H (2005) Infection and inflammation in cystic fibrosis: a short review. J Cyst Fibros 4(Suppl 2):3–5. doi:10.1016/j.jcf.2005.05.005 PubMedCrossRef

221.

Mott LS, Park J, Murray CP et al (2012) Progression of early structural lung disease in young children with cystic fibrosis assessed using CT. Thorax 67:509–516. doi:10.1136/thoraxjnl-2011-200912 PubMedCrossRef

222.

Lipuma JJ (2010) The changing microbial epidemiology in cystic fibrosis. Clin Microbiol Rev 23:299–323. doi:10.1128/CMR.00068-09 PubMedPubMedCentralCrossRef

223.

Cohen TS, Prince A (2012) Cystic fibrosis: a mucosal immunodeficiency syndrome. Nat Med 18:509–519. doi:10.1038/nm.2715 PubMedPubMedCentralCrossRef

224.

Adriaanse MPM, van der Sande LJTM, van den Neucker AM et al (2015) Evidence for a cystic fibrosis enteropathy. PLoS One 10:e0138062. doi:10.1371/journal.pone.0138062 PubMedPubMedCentralCrossRef

225.

Ramsey BW, Davies J, McElvaney NG et al (2011) A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 365:1663–1672. doi:10.1056/NEJMoa1105185 PubMedPubMedCentralCrossRef

226.

Painter RG, Valentine VG, Lanson NA et al (2006) CFTR expression in human neutrophils and the phagolysosomal chlorination defect in cystic fibrosis. Biochemistry 45:10260–10269. doi:10.1021/bi060490t PubMedPubMedCentralCrossRef

227.

Moriceau S, Lenoir G, Witko-Sarsat V (2010) In cystic fibrosis homozygotes and heterozygotes, neutrophil apoptosis is delayed and modulated by diamide or roscovitine: evidence for an innate neutrophil disturbance. J Innate Immun 2:260–266. doi:10.1159/000295791 PubMedCrossRef

228.

Vandivier RW, Fadok VA, Hoffmann PR et al (2002) Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J Clin Invest 109:661–670. doi:10.1172/JCI13572 PubMedPubMedCentralCrossRef

229.

Sedor J, Hogue L, Akers K et al (2007) Cathepsin-G interferes with clearance of Pseudomonas aeruginosa from mouse lungs. Pediatr Res 61:26–31. doi:10.1203/01.pdr.0000250043.90468.c2 PubMedCrossRef

230.

Konstan MW, Byard PJ, Hoppel CL, Davis PB (1995) Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med 332:848–854. doi:10.1056/NEJM199503303321303 PubMedCrossRef

231.

Ren CL, Pasta DJ, Rasouliyan L et al (2008) Relationship between inhaled corticosteroid therapy and rate of lung function decline in children with cystic fibrosis. J Pediatr 153:746–751. doi:10.1016/j.jpeds.2008.07.010 PubMedCrossRef

232.

Pizzutto SJ, Upham JW, Yerkovich ST, Chang AB (2010) Inhaled non-steroid anti-inflammatories for children and adults with bronchiectasis. Cochrane Database Syst Rev CD007525. doi: 10.1002/14651858.CD007525.pub2

233.

Konstan MW, Walenga RW, Hilliard KA, Hilliard JB (1993) Leukotriene B4 markedly elevated in the epithelial lining fluid of patients with cystic fibrosis. Am Rev Respir Dis 148:896–901. doi:10.1164/ajrccm/148.4_Pt_1.896 PubMedCrossRef

234.

Stelmach I, Korzeniewska A, Stelmach W et al (2005) Effects of montelukast treatment on clinical and inflammatory variables in patients with cystic fibrosis. Ann Allergy Asthma Immunol 95:372–380. doi:10.1016/S1081-1206(10)61156-8 PubMedCrossRef

235.

Tateda K, Ishii Y, Matsumoto T et al (2000) Potential of macrolide antibiotics to inhibit protein synthesis of Pseudomonas aeruginosa: suppression of virulence factors and stress response. J Infect Chemother 6:1–7. doi:10.1007/s101560000013 PubMedCrossRef

236.

Schultz MJ (2004) Macrolide activities beyond their antimicrobial effects: macrolides in diffuse panbronchiolitis and cystic fibrosis. J Antimicrob Chemother 54:21–28. doi:10.1093/jac/dkh309 PubMedCrossRef

237.

Southern KW, Barker PM, Solis-Moya A, Patel L (2012) Macrolide antibiotics for cystic fibrosis. Cochrane Database Syst Rev 11:CD002203. doi:10.1002/14651858.CD002203.pub4 PubMed

238.

Zarogoulidis P, Papanas N, Kioumis I et al (2012) Macrolides: from in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases. Eur J Clin Pharmacol 68:479–503. doi:10.1007/s00228-011-1161-x PubMedCrossRef

239.

Binder AM, Adjemian J, Olivier KN, Prevots DR (2013) Epidemiology of nontuberculous mycobacterial infections and associated chronic macrolide use among persons with cystic fibrosis. Am J Respir Crit Care Med 188:807–812. doi:10.1164/rccm.201307-1200OC PubMedPubMedCentralCrossRef

240.

Jouneau S, Bonizec M, Belleguic C et al (2011) Anti-inflammatory effect of fluvastatin on IL-8 production induced by Pseudomonas aeruginosa and Aspergillus fumigatus antigens in cystic fibrosis. PLoS One 6:e22655. doi:10.1371/journal.pone.0022655 PubMedPubMedCentralCrossRef

241.

Ilmarinen P, Kankaanranta H (2014) Eosinophil apoptosis as a therapeutic target in allergic asthma. Basic Clin Pharmacol Toxicol 114:109–117. doi:10.1111/bcpt.12163 PubMedCrossRef

242.

Joos S, Miksch A, Szecsenyi J et al (2008) Montelukast as add-on therapy to inhaled corticosteroids in the treatment of mild to moderate asthma: a systematic review. Thorax 63:453–462. doi:10.1136/thx.2007.081596 PubMedCrossRef

243.

Duffin R, Leitch AE, Sheldrake TA et al (2009) The CDK inhibitor, R-roscovitine, promotes eosinophil apoptosis by down-regulation of Mcl-1. FEBS Lett 583:2540–2546. doi:10.1016/j.febslet.2009.07.017 PubMedCrossRef

244.

Alessandri AL, Duffin R, Leitch AE et al (2011) Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation. PLoS One 6:e25683. doi:10.1371/journal.pone.0025683 PubMedPubMedCentralCrossRef

245.

Farahi N, Uller L, Juss JK et al (2011) Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearance. Clin Exp Allergy 41:673–687. doi:10.1111/j.1365-2222.2010.03680.x PubMedCrossRef

246.

Reis AC, Alessandri AL, Athayde RM et al (2015) Induction of eosinophil apoptosis by hydrogen peroxide promotes the resolution of allergic inflammation. Cell Death Dis 6, e1632. doi:10.1038/cddis.2014.580 PubMedPubMedCentralCrossRef

247.

Starosta V, Pazdrak K, Boldogh I et al (2008) Lipoxin A4 counterregulates GM-CSF signaling in eosinophilic granulocytes. J Immunol 181:8688–8699PubMedPubMedCentralCrossRef

248.

Karra L, Haworth O, Priluck R et al (2015) Lipoxin B₄ promotes the resolution of allergic inflammation in the upper and lower airways of mice. Mucosal Immunol 8:852–862. doi:10.1038/mi.2014.116 PubMedCrossRef

249.

Polier G, Ding J, Konkimalla BV et al (2011) Wogonin and related natural flavones are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1. Cell Death Dis 2, e182. doi:10.1038/cddis.2011.66 PubMedPubMedCentralCrossRef

250.

Lucas CD, Allen KC, Dorward DA et al (2013) Flavones induce neutrophil apoptosis by down-regulation of Mcl-1 via a proteasomal-dependent pathway. Faseb J 27:1084–94. doi:10.1096/fj.12-218990, Epub 2012 Nov 29PubMedPubMedCentralCrossRef

251.

Lucas CD, Dorward DA, Sharma S et al (2015) Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation. Am J Respir Crit Care Med 191:626–636. doi:10.1164/rccm.201408-1565OC PubMedPubMedCentralCrossRef

Title: Key mechanisms governing resolution of lung inflammation
Authors: C. T. Robb
K. H. Regan
D. A. Dorward
A. G. Rossi
Publication date: 01-07-2016
Publisher: Springer Berlin Heidelberg
Published in: Seminars in Immunopathology / Issue 4/2016
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-016-0560-6

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