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Overview of Innate Lung Immunity and Inflammation

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Lung Innate Immunity and Inflammation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1809))

Abstract

The nasal passages, conducting airways and gas-exchange surfaces of the lung, are constantly exposed to substances contained in the air that we breathe. While many of these suspended substances are relatively harmless, some, for example, pathogenic microbes, noxious pollutants, and aspirated gastric contents can be harmful. The innate immune system, lungs and conducting airways have evolved specialized mechanisms to protect the respiratory system not only from these harmful inhaled substances but also from the overly exuberant innate immune activation that can arise during the host response to harmful inhaled substances. Herein, we discuss the cell types that contribute to lung innate immunity and inflammation and how their activities are coordinated to promote lung health.

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References

  1. Bals R et al (1998) Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 102(5):874–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bals R et al (1998) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci U S A 95(16):9541–9546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Garcia JR et al (2001) Human beta-defensin 4: a novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity. FASEB J 15(10):1819–1821

    Article  CAS  PubMed  Google Scholar 

  4. Goldman MJ et al (1997) Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88(4):553–560

    Article  CAS  PubMed  Google Scholar 

  5. Jia HP et al (2001) Discovery of new human beta-defensins using a genomics-based approach. Gene 263(1-2):211–218

    Article  CAS  PubMed  Google Scholar 

  6. Singh PK et al (1998) Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci U S A 95(25):14,961–14,966

    Article  CAS  Google Scholar 

  7. Alekseeva L et al (2009) Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatus organisms. BMC microbiology 9:33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Beisswenger C, Bals R (2005) Functions of antimicrobial peptides in host defense and immunity. Curr Protein Pept Sci 6(3):255–264

    Article  CAS  PubMed  Google Scholar 

  9. Harder J et al (2000) Mucoid pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia. Am J Respir Cell Mol Biol 22(6):714–721

    Article  CAS  PubMed  Google Scholar 

  10. Thompson AB et al (1990) Lower respiratory tract lactoferrin and lysozyme arise primarily in the airways and are elevated in association with chronic bronchitis. J Lab Clin Med 115(2):148–158

    PubMed  CAS  Google Scholar 

  11. Zhao YX et al (2000) Secretion of complement components of the alternative pathway (C3 and factor B) by the human alveolar type II epithelial cell line A549. Int J Mol Med 5(4):415–419

    PubMed  CAS  Google Scholar 

  12. Becker MN et al (2000) CD14-dependent lipopolysaccharide-induced beta-defensin-2 expression in human tracheobronchial epithelium. J Biol Chem 275(38):29731–29736

    Article  CAS  PubMed  Google Scholar 

  13. Diamond G, Legarda D, Ryan LK (2000) The innate immune response of the respiratory epithelium. Immunol Rev 173:27–38

    Article  CAS  PubMed  Google Scholar 

  14. Jany B, Betz R, Schreck R (1995) Activation of the transcription factor NF-kappa B in human tracheobronchial epithelial cells by inflammatory stimuli. Eur Respir J 8(3):387–391

    Article  CAS  PubMed  Google Scholar 

  15. Jaspers I, Flescher E, Chen LC (1997) Ozone-induced IL-8 expression and transcription factor binding in respiratory epithelial cells. Am J Physiol 272(3 Pt 1):L504–L511

    PubMed  CAS  Google Scholar 

  16. Janssen YM et al (1995) Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells. Proc Natl Acad Sci U S A 92(18):8458–8462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Takizawa H et al (1999) Diesel exhaust particles induce NF-kappa B activation in human bronchial epithelial cells in vitro: importance in cytokine transcription. J Immunol 162(8):4705–4711

    PubMed  CAS  Google Scholar 

  18. Quay JL et al (1998) Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-kappaB activation. Am J Respir Cell Mol Biol 19(1):98–106

    Article  CAS  PubMed  Google Scholar 

  19. Platz J et al (2004) Microbial DNA induces a host defense reaction of human respiratory epithelial cells. J Immunol 173(2):1219–1223

    Article  CAS  PubMed  Google Scholar 

  20. Skerrett SJ et al (2004) Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin. Am J Physiol Lung Cell Mol Physiol 287(1):L143–L152

    Article  CAS  PubMed  Google Scholar 

  21. Hajjar AM et al (2005) An essential role for non-bone marrow-derived cells in control of Pseudomonas aeruginosa pneumonia. Am J Respir Cell Mol Biol 33(5):470–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cowburn AS et al (2008) Advances in neutrophil biology: clinical implications. Chest 134(3):606–612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nathan C (2006) Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6(3):173–182

    Article  CAS  Google Scholar 

  24. Wang Q, Doerschuk CM, Mizgerd JP (2004) Neutrophils in innate immunity. Semin Respir Crit Care Med 25(1):33–41

    Article  PubMed  Google Scholar 

  25. Sittipunt C et al (2001) Nitric oxide and nitrotyrosine in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 163(2):503–510

    Article  CAS  PubMed  Google Scholar 

  26. Oppenheim JJ et al (2007) Alarmins initiate host defense. Adv Exp Med Biol 601:185–194

    Article  PubMed  Google Scholar 

  27. Wang J et al (2017) Visualizing the function and fate of neutrophils in sterile injury and repair. Science 358(6359):111–116

    Article  CAS  Google Scholar 

  28. Furze RC, Rankin SM (2008) The role of the bone marrow in neutrophil clearance under homeostatic conditions in the mouse. FASEB J 22(9):3111–3119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Suratt BT et al (2001) Neutrophil maturation and activation determine anatomic site of clearance from circulation. Am J Physiol Lung Cell Mol Physiol 281(4):L913–L921

    Article  CAS  PubMed  Google Scholar 

  30. Furze RC, Rankin SM (2008) Neutrophil mobilization and clearance in the bone marrow. Immunology 125(3):281–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Doherty DE et al (1992) Prolonged monocyte accumulation in the lung during bleomycin-induced pulmonary fibrosis. A noninvasive assessment of monocyte kinetics by scintigraphy. Lab Invest 66(2):231–242

    PubMed  CAS  Google Scholar 

  32. Harmsen AG et al (1985) The role of macrophages in particle translocation from lungs to lymph nodes. Science 230(4731):1277–1280

    Article  CAS  PubMed  Google Scholar 

  33. Kitamura T et al (1999) Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor. J Exp Med 190(6):875–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Martin RJ et al (1980) Pulmonary alveolar proteinosis: the diagnosis by segmental lavage. Am Rev Respir Dis 121(5):819–825

    PubMed  CAS  Google Scholar 

  35. Nugent KM, Pesanti EL (1983) Macrophage function in pulmonary alveolar proteinosis. Am Rev Respir Dis 127(6):780–781

    PubMed  CAS  Google Scholar 

  36. Holt PG (1978) Inhibitory activity of unstimulated alveolar macrophages on T-lymphocyte blastogenic response. The American review of respiratory disease 118(4):791–793

    Article  CAS  PubMed  Google Scholar 

  37. Toews GB et al (1984) The accessory cell function of human alveolar macrophages in specific T cell proliferation. Journal of immunology 132(1):181–186

    CAS  Google Scholar 

  38. Gardai SJ et al (2003) By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 115(1):13–23

    Article  CAS  PubMed  Google Scholar 

  39. Morris DG et al (2003) Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Nature 422(6928):169–173

    Article  CAS  PubMed  Google Scholar 

  40. Munger JS et al (1999) The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96(3):319–328

    Article  CAS  PubMed  Google Scholar 

  41. Kawabe T et al (1992) Immunosuppressive activity induced by nitric oxide in culture supernatant of activated rat alveolar macrophages. Immunology 76(1):72–78

    PubMed  PubMed Central  CAS  Google Scholar 

  42. Roth MD, Golub SH (1993) Human pulmonary macrophages utilize prostaglandins and transforming growth factor beta 1 to suppress lymphocyte activation. Journal of leukocyte biology 53(4):366–371

    Article  CAS  PubMed  Google Scholar 

  43. Bilyk N, Holt PG (1993) Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor. J Exp Med 177(6):1773–1777

    Article  CAS  PubMed  Google Scholar 

  44. Bromley SK, Mempel TR, Luster AD (2008) Orchestrating the orchestrators: chemokines in control of T cell traffic. Nat Immunol 9(9):970–980

    Article  CAS  PubMed  Google Scholar 

  45. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76(2):301–314

    Article  CAS  Google Scholar 

  46. Mould KJ et al (2017) Cell origin dictates programming of resident versus recruited macrophages during acute lung injury. Am J Respir Cell Mol Biol 57(3):294–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vignais PV (2002) The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cellular and molecular life sciences : CMLS 59(9):1428–1459

    Article  CAS  PubMed  Google Scholar 

  48. Chang YC et al (1998) Virulence of catalase-deficient aspergillus nidulans in p47(phox)−/− mice. Implications for fungal pathogenicity and host defense in chronic granulomatous disease. J Clin Invest 101(9):1843–1850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Jackson SH, Gallin JI, Holland SM (1995) The p47phox mouse knock-out model of chronic granulomatous disease. J Exp Med 182(3):751–758

    Article  CAS  PubMed  Google Scholar 

  50. Kelly JK et al (1986) Fatal Aspergillus pneumonia in chronic granulomatous disease. Am J Clin Pathol 86(2):235–240

    Article  CAS  PubMed  Google Scholar 

  51. Tauber AI et al (1983) Chronic granulomatous disease: a syndrome of phagocyte oxidase deficiencies. Medicine 62(5):286–309

    Article  CAS  PubMed  Google Scholar 

  52. Castranova V (1994) Generation of oxygen radicals and mechanisms of injury prevention. Environ Health Perspect 102(Suppl 10):65–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fireman E et al (1989) Suppressive activity of alveolar macrophages and blood monocytes from interstitial lung diseases: role of released soluble factors. Int J Immunopharmacol 11(7):751–760

    Article  CAS  PubMed  Google Scholar 

  54. Gossart S et al (1996) Reactive oxygen intermediates as regulators of TNF-alpha production in rat lung inflammation induced by silica. J Immunol 156(4):1540–1548

    PubMed  CAS  Google Scholar 

  55. Kondo T et al (1994) Current smoking of elderly men reduces antioxidants in alveolar macrophages. American J Respir Crit Care Med 149(1):178–182

    Article  CAS  Google Scholar 

  56. Lake FR et al (1994) Functional switching of macrophage responses to tumor necrosis factor-alpha (TNF alpha) by interferons. Implications for the pleiotropic activities of TNF alpha. J Clin Invest 93(4):1661–1669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Laszlo DJ et al (1993) Development of functional diversity in mouse macrophages. Mutual exclusion of two phenotypic states. Am J Pathol 143(2):587–597

    PubMed  PubMed Central  CAS  Google Scholar 

  58. Noble PW et al (1993) Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages. J Clin Invest 91(6):2368–2377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Riches DW et al (1988) Differential regulation of gene expression during macrophage activation with a polyribonucleotide. The role of endogenously derived IFN. J Immunol 141(1):180–188

    PubMed  CAS  Google Scholar 

  60. Stout RD et al (2005) Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J Immunol 175(1):342–349

    Article  CAS  PubMed  Google Scholar 

  61. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3(1):23–35

    Article  CAS  PubMed  Google Scholar 

  62. Riches DW (1995) Signalling heterogeneity as a contributing factor in macrophage functional diversity. Semin Cell Biol 6(6):377–384

    Article  CAS  PubMed  Google Scholar 

  63. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8(12):958–969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Mantovani A et al (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23(11):549–555

    Article  CAS  PubMed  Google Scholar 

  65. Mantovani A et al (2013) Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol 229(2):176–185

    Article  CAS  PubMed  Google Scholar 

  66. Ramachandran P et al (2012) Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc Natl Acad Sci U S A 109(46):E3186–E3195

    Article  PubMed  PubMed Central  Google Scholar 

  67. Martinez FO et al (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 177(10):7303–7311

    Article  CAS  PubMed  Google Scholar 

  68. Murray PJ, Wynn TA (2011) Obstacles and opportunities for understanding macrophage polarization. J Leukoc Biol 89(4):557–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122(3):787–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Lawrence T, Natoli G (2011) Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol 11(11):750–761

    Article  CAS  PubMed  Google Scholar 

  71. Banerjee S et al (2013) MicroRNA let-7c regulates macrophage polarization. J Immunol 190(12):6542–6549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Graff JW et al (2012) Identifying functional microRNAs in macrophages with polarized phenotypes. J Biol Chem 287(26):21816–21825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Liu G, Abraham E (2013) MicroRNAs in immune response and macrophage polarization. Arterioscler Thromb Vasc Biol 33(2):170–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Shibata Y et al (2001) Alveolar macrophage deficiency in osteopetrotic mice deficient in macrophage colony-stimulating factor is spontaneously corrected with age and associated with matrix metalloproteinase expression and emphysema. Blood 98(9):2845–2852

    Article  CAS  PubMed  Google Scholar 

  75. Thepen T, Van Rooijen N, Kraal G (1989) Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. J Exp Med 170(2):499–509

    Article  CAS  PubMed  Google Scholar 

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Conflicts of Interest

DWHR has no conflicts of interest to declare. TRM has no conflicts of interest to declare.

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Authors and Affiliations

  1. Program in Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA

    David W. H. Riches

  2. Division of Pulmonary, Critical and Sleep Medicine, University of Washington School of Medicine, Seattle, WA, USA

    Thomas R. Martin

Authors
  1. David W. H. Riches
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  2. Thomas R. Martin
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Correspondence to David W. H. Riches .

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Editors and Affiliations

  1. Department of Immunology and Microbiology University of Colorado School of Medicine, Department of Biomedical Research and Center for Genes Environment and Health, National Jewish Health Denver, CO, USA, Aurora,, Colorado, USA

    Scott Alper

  2. Division of Pulmonary Sciences and Critical Care Medicine Department of Medicine University of Colorado Denver, Division of Pulmonary, Critical Care and Sleep Medicine Department of Medicine National Jewish Health Denver, CO, USA, Aurora, Colorado, USA

    William J. Janssen

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Riches, D.W.H., Martin, T.R. (2018). Overview of Innate Lung Immunity and Inflammation. In: Alper, S., Janssen, W. (eds) Lung Innate Immunity and Inflammation. Methods in Molecular Biology, vol 1809. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8570-8_2

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  • DOI: https://doi.org/10.1007/978-1-4939-8570-8_2

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8569-2

  • Online ISBN: 978-1-4939-8570-8

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