Skip to main content

Advertisement

Log in

Eosinophils and asthma

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Recruitment and activation of eosinophils into the airways of asthma patients is suggested to be a contributing causative agent in the histopathologies and lung dysfunction that are characteristic of asthma. Recent studies in mouse models of asthma and in human patients implicate eosinophils in immune regulation and remodeling in the lung in addition to their hypothesized role as destructive agents. Specifically, eosinophils not only participate in release of granule proteins, lipid mediators, reactive oxygen species, cytokines, and growth factors but also function through complex cell-cell interactions to elicit chronic T helper 2 inflammation in the lung. This review highlights the roles of eosinophils in asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Lemanske RF Jr, Busse WW: 6. Asthma: Factors underlying inception, exacerbation, and disease progression. J Allergy Clin Immunol 2006, 117:S456–S461.

    Article  PubMed  CAS  Google Scholar 

  2. Larche M, Robinson DS, Kay AB: The role of T lymphocytes in the pathogenesis of asthma. J Allergy Clin Immunol 2003, 111:450–463; quiz 464.

    Article  PubMed  CAS  Google Scholar 

  3. Miyahara N, Swanson BJ, Takeda K, et al.: Effector CD8(+) T cells mediate inflammation and airway hyperresponsiveness. Nat Med 2004, 10:865–869.

    Article  PubMed  CAS  Google Scholar 

  4. Akbari O, Faul JL, Hoyte EG, et al.: CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N Engl J Med 2006, 354:1117–1129.

    Article  PubMed  CAS  Google Scholar 

  5. Huber HL, Koessler KK: The pathology of bronchial asthma. Arch Intern Med 1922, 30:689–760.

    Google Scholar 

  6. Tomassini M, Tsicopoulos A, Tai PC, et al.: Release of granule proteins by eosinophils from allergic and nonallergic patients with eosinophilia on immunoglobulin-dependent activation. J Allergy Clin Immunol 1991, 88:365–375.

    Article  PubMed  CAS  Google Scholar 

  7. Bousquet J, Chanez P, Lacoste JY, et al.: Eosinophilic inflammation in asthma. N Engl J Med 1990, 323:1033–1039. [Comment in N Engl J Med 1991, 324:1514–1515.]

    Article  PubMed  CAS  Google Scholar 

  8. Stelmach I, Majak P, Grzelewski T, et al.: The ECP/Eo count ratio in children with asthma. J Asthma 2004, 41:539–546.

    Article  PubMed  CAS  Google Scholar 

  9. Venge P: Monitoring the allergic inflammation. Allergy 2004, 59:26–32.

    Article  PubMed  CAS  Google Scholar 

  10. Bradley A: Mining the mouse genome. Nature 2002, 420:512–514.

    Article  PubMed  CAS  Google Scholar 

  11. Sanderson CJ: Interleukin-5 and the regulation of eosinophil production. In Immunopharmacology of Eosinophils. Edited by Smith H, Cook RM. Epsom, Surrey, UK: Academic Press; 1993:11–24.

    Google Scholar 

  12. Mathur M, Herrmann K, Li X, et al.: TRFK-5 reverses established airway eosinophilia but not established hyperresponsiveness in a murine model of chronic asthma. Am J Respir Crit Care Med 1999, 159:580–587.

    PubMed  CAS  Google Scholar 

  13. Lee JJ, McGarry MP, Farmer SC, et al.: Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J Exp Med 1997, 185:2143–2156.

    Article  PubMed  CAS  Google Scholar 

  14. Zhu Z, Homer RJ, Wang Z, et al.: Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999, 103:779–788.

    PubMed  CAS  Google Scholar 

  15. Kanehiro A, Takeda K, Joetham A, et al.: Timing of administration of anti-VLA-4 differentiates airway hyperresponsiveness in the central and peripheral airways in mice. Am J Respir Crit Care Med 2000, 162:1132–1139.

    PubMed  CAS  Google Scholar 

  16. Henderson WR Jr, Chiang GK, Tien YT, Chi EY: Reversal of allergen-induced airway remodeling by CysLT1 receptor blockade. Am J Respir Crit Care Med 2006, 173:718–728.

    Article  PubMed  CAS  Google Scholar 

  17. Shen HH, Ochkur SI, McGarry MP, et al.: A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse. J Immunol 2003, 170:3296–3305.

    PubMed  CAS  Google Scholar 

  18. Justice JP, Borchers MT, Crosby JR, et al.: Ablation of eosinophils leads to a reduction of allergen-induced pulmonary pathology. Am J Physiol Lung Cell Mol Physiol 2003, 284:L169–178.

    PubMed  CAS  Google Scholar 

  19. Lee JJ, Dimina D, Macias MP, et al.: Defining a link with asthma in mice congenitally deficient in eosinophils. Science 2004, 305:1773–1776.

    Article  PubMed  CAS  Google Scholar 

  20. Humbles AA, Lloyd CM, McMillan SJ, et al.: A critical role for eosinophils in allergic airways remodeling. Science 2004, 305:1776–1779.

    Article  PubMed  CAS  Google Scholar 

  21. Leckie MJ, ten Brinke A, Khan J, et al.: Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000, 356:2144–2148.

    Article  PubMed  CAS  Google Scholar 

  22. O’Byrne PM, Inman MD, Parameswaran K: The trials and tribulations of IL-5, eosinophils, and allergic asthma. J Allergy Clin Immunol 2001, 108:503–508.

    Article  PubMed  CAS  Google Scholar 

  23. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS: Eosinophil’s role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 2003, 167:199–204.

    Article  PubMed  Google Scholar 

  24. Flood-Page P, Menzies-Gow A, Phipps S, et al.: Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest 2003, 112:1029–1036.

    Article  PubMed  CAS  Google Scholar 

  25. Wardlaw AJ: Eosinophil trafficking in asthma. Clin Med 2001, 1:214–218.

    PubMed  CAS  Google Scholar 

  26. Pitchford SC, Momi S, Giannini S, et al.: Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation. Blood 2005, 105:2074–2081.

    Article  PubMed  CAS  Google Scholar 

  27. Ying S, Meng Q, Zeibecoglou K, et al.: Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics. J Immunol 1999, 163:6321–6329.

    PubMed  CAS  Google Scholar 

  28. Teixeira MM, Giembycz MA, Lindsay MA, Hellewell PG: Pertussis toxin shows distinct early signaling events in platelet-activating factor-, leukotriene B4-, and C5a-induced eosinophil homotypic aggregation in vitro and recruitment in vivo. Blood 1997, 89:4566–4573.

    PubMed  CAS  Google Scholar 

  29. Southam DS, Widmer N, Ellis R, et al.: Increased eosinophil-lineage committed progenitors in the lung of allergen-challenged mice. J Allergy Clin Immunol 2005, 115:95–102.

    Article  PubMed  CAS  Google Scholar 

  30. Gleich GJ, Adolphson CR: The eosinophil and bronchial asthma: evidence for a critical role of eosinophils in pathophysiology. In Interleukin-5: From Molecule to Drug Target for Asthma. Edited by Sanderson CJ. New York: Marcel Dekker; 1999:1–37.

    Google Scholar 

  31. Lee JJ, Lee NA: Eosinophil degranulation: an evolutionary vestige or a universally destructive effector function? Clin Exper Allergy 2005, 35:986–994.

    Article  CAS  Google Scholar 

  32. Walsh GM: Eosinophil granule proteins and their role in disease. Curr Opin Hematol 2001, 8:28–33.

    Article  PubMed  CAS  Google Scholar 

  33. Brottman GM, Regelmann WE, Slungaard A, Wangensteen OD: Effect of eosinophil peroxidase on airway epithelial permeability in the guinea pig. Pediatr Pulmonol 1996, 21:159–166.

    Article  PubMed  CAS  Google Scholar 

  34. Rochester CL, Ackerman SJ, Zheng T, Elias JA: Eosinophilfibroblast interactions: granule major basic protein interacts with IL-1 and transforming growth factor-beta in the stimulation of lung fibroblast IL-6-type cytokine production. J Immunol 1996, 156:4449–4456.

    PubMed  CAS  Google Scholar 

  35. Rabe KF, Munoz NM, Vita AJ, et al.: Contraction of human bronchial smooth muscle caused by activated human eosinophils. Am J Physiol 1994, 267:L326–334.

    PubMed  CAS  Google Scholar 

  36. Evans CM, Fryer AD, Jacoby DB, et al.: Pretreatment with antibody to eosinophil major basic protein prevents hyperresponsiveness by protecting neuronal M2 muscarinic receptors in antigen-challenged guinea pigs. J Clin Invest 1997, 100:2254–2262.

    Article  PubMed  CAS  Google Scholar 

  37. Wang JG, Mahmud SA, Thompson JA, et al.: The principal eosinophil peroxidase product, HOSCN, is a uniquely potent phagocyte oxidant inducer of endothelial cell tissue factor activity: a potential mechanism for thrombosis in eosinophilic inflammatory states. Blood 2006, 107:558–565.

    Article  PubMed  CAS  Google Scholar 

  38. Haskell MD, Moy JN, Gleich GJ, Thomas LL: Analysis of signaling events associated with activation of neutrophil superoxide anion production by eosinophil granule major basic protein. Blood 1995, 86:4627–4637.

    PubMed  CAS  Google Scholar 

  39. Piliponsky AM, Pickholtz D, Gleich GJ, Levi-Schaffer F: Human eosinophils induce histamine release from antigen-activated rat peritoneal mast cells: a possible role for mast cells in late-phase allergic reactions. J Allergy Clin Immunol 2001, 107:993–1000.

    Article  PubMed  CAS  Google Scholar 

  40. Voehringer D, Shinkai K, Locksley RM: Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity 2004, 20:267–277.

    Article  PubMed  CAS  Google Scholar 

  41. Justice JP, Borchers MT, Lee JJ, et al.: Ragweed-induced expression of GATA-3, IL-4, and IL-5 by eosinophils in the lungs of allergic C57BL/6J mice. Am J Physiol Lung Cell Mol Physiol 2002, 282:L302–309.

    PubMed  CAS  Google Scholar 

  42. Lamkhioued B, Gounni AS, Aldebert D, et al.: Synthesis of type 1 (IFN gamma) and type 2 (IL-4, IL-5, and IL-10) cytokines by human eosinophils. Ann N Y Acad Sci 1996, 796:203–208.

    Article  PubMed  CAS  Google Scholar 

  43. Lim KG, Wan HC, Resnick M, et al.: Human eosinophils release the lymphocyte and eosinophil active cytokines, RANTES and lymphocyte chemoattractant factor. Int Arch Allergy Immunol 1995, 107:342.

    Article  PubMed  CAS  Google Scholar 

  44. Shi HZ, Humbles A, Gerard C, et al.: Lymph node trafficking and antigen presentation by endobronchial eosinophils. J Clin Invest 2000, 105:945–953.

    PubMed  CAS  Google Scholar 

  45. MacKenzie JR, Mattes J, Dent LA, Foster PS: Eosinophils promote allergic disease of the lung by regulating CD4+ Th2 lymphocyte function. J Immunol 2001, 167:3146–3155.

    PubMed  CAS  Google Scholar 

  46. Odemuyiwa SO, Ghahary A, Li Y, et al.: Cutting edge: human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase. J Immunol 2004, 173:5909–5913.

    PubMed  CAS  Google Scholar 

  47. Mitra SN, Slungaard A, Hazen SL: Role of eosinophil peroxidase in the origins of protein oxidation in asthma. Redox Rep 2000, 5:215–224.

    Article  PubMed  CAS  Google Scholar 

  48. Kaminsky DA, Mitchell J, Carroll N, et al.: Nitrotyrosine formation in the airways and lung parenchyma of patients with asthma. J Allergy Clin Immunol 1999, 104:747–754.

    Article  PubMed  CAS  Google Scholar 

  49. Berry MA, Shaw DE, Green RH, et al.: The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma. Clin Exp Allergy 2005, 35:1175–1179.

    Article  PubMed  CAS  Google Scholar 

  50. Bandeira-Melo C, Bozza PT, Weller PF: The cellular biology of eosinophil eicosanoid formation and function. J Allergy Clin Immunol 2002, 109:393–400.

    Article  PubMed  CAS  Google Scholar 

  51. Lee T, Lenihan DJ, Malone B, et al.: Increased biosynthesis of platelet-activating factor in activated human eosinophils. J Biol Chem 1984, 259:5526–5530.

    PubMed  CAS  Google Scholar 

  52. Weller PF, Lee CW, Foster DW, et al.: Generation and metabolism of 5-lipoxygenase pathway leukotrienes by human eosinophils: predominant production of leukotriene C4. Proc Natl Acad Sci U S A 1983, 80:7626–7630.

    Article  PubMed  CAS  Google Scholar 

  53. Carey MA, Germolec DR, Langenbach R, Zeldin DC: Cyclooxygenase enzymes in allergic inflammation and asthma. Prostaglandins Leukot Essent Fatty Acids 2003, 69:157–162.

    Article  PubMed  CAS  Google Scholar 

  54. Luster AD, Tager AM: T-cell trafficking in asthma: lipid mediators grease the way. Nat Rev Immunol 2004, 4:711–724.

    Article  PubMed  CAS  Google Scholar 

  55. Nagata M, Saito K: The roles of cysteinyl leukotrienes in eosinophilic inflammation of asthmatic airways. Int Arch Allergy Immunol 2003, 131(Suppl 1):7–10.

    Article  PubMed  CAS  Google Scholar 

  56. Uhlig S, Wollin L, Wendel A: Contributions of thromboxane and leukotrienes to PAF-induced impairment of lung function in the rat. J Appl Physiol 1994, 77:262–269.

    PubMed  CAS  Google Scholar 

  57. Dahlen SE, Hedqvist P, Hammarstrom S, Samuelsson B: Leukotrienes are potent constrictors of human bronchi. Nature 1980, 288:484–486.

    Article  PubMed  CAS  Google Scholar 

  58. Mita H, Hasegawa M, Saito H, Akiyama K: Levels of cysteinyl leukotriene receptor mRNA in human peripheral leucocytes: significantly higher expression of cysteinyl leukotriene receptor 2 mRNA in eosinophils. Clin Exp Allergy 2001, 31:1714–1723.

    Article  PubMed  CAS  Google Scholar 

  59. Fujii M, Tanaka H, Abe S: Interferon-gamma up-regulates expression of cysteinyl leukotriene type 2 receptors on eosinophils in asthmatic patients. Chest 2005, 128:3148–3155.

    Article  PubMed  CAS  Google Scholar 

  60. Williams TJ: The eosinophil enigma. J Clin Invest 2004, 113:507–509.

    Article  PubMed  CAS  Google Scholar 

  61. Pascual RM, Peters SP: Airway remodeling contributes to the progressive loss of lung function in asthma: an overview. J Allergy Clin Immunol 2005, 116:477–486.

    Article  PubMed  Google Scholar 

  62. Tschumperlin DJ, Drazen JM: Chronic effects of mechanical force on airways. Annu Rev Physiol 2006, 68:563–583.

    Article  PubMed  CAS  Google Scholar 

  63. Cho JY, Miller M, Baek KJ, et al.: Inhibition of airway remodeling in IL-5-deficient mice. J Clin Invest 2004, 113:551–560.

    Article  PubMed  CAS  Google Scholar 

  64. Minshall EM, Leung DY, Martin RJ, et al.: Eosinophil-associated TGF-betal mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 1997, 17:326–333.

    PubMed  CAS  Google Scholar 

  65. Horiuchi T, Weller PF: Expression of vascular endothelial growth factor by human eosinophils: upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5. Am J Respir Cell Mol Biol 1997, 17:70–77.

    PubMed  CAS  Google Scholar 

  66. Stenfeldt AL, Wenneras C: Danger signals derived from stressed and necrotic epithelial cells activate human eosinophils. Immunology 2004, 112:605–614.

    Article  PubMed  CAS  Google Scholar 

  67. Kobayashi H, Gleich GJ, Butterfield JH, Kita H: Human eosinophils produce neurotrophins and secrete nerve growth factor on immunologic stimuli. Blood 2002, 99:2214–2220.

    Article  PubMed  CAS  Google Scholar 

  68. Ohno I, Nitta Y, Yamauchi K, et al.: Eosinophils as a potential source of platelet-derived growth factor B-chain (PDGF-B) in nasal polyposis and bronchial asthma. Am J Respir Cell Mol Biol 1995, 13:639–647.

    PubMed  CAS  Google Scholar 

  69. Wiehler S, Cuvelier SL, Chakrabarti S, Patel KD: p38 MAP kinase regulates rapid matrix metalloproteinase-9 release from eosinophils. Biochem Biophys Res Commun 2004, 315:463–470.

    Article  PubMed  CAS  Google Scholar 

  70. Kelly EA, Busse WW, Jarjour NN: Increased matrix metalloproteinase-9 in the airway after allergen challenge. Am J Respir Crit Care Med 2000, 162(3 Pt 1):1157–1161.

    PubMed  CAS  Google Scholar 

  71. Pope SM, Fulkerson PC, Blanchard C, et al.: Identification of a cooperative mechanism involving IL-13 and eotaxin-2 in experimental allergic lung inflammation. J Biol Chem 2005, 280:13952–13961.

    Article  PubMed  CAS  Google Scholar 

  72. Teran LM, Mochizuki M, Bartels J, et al.: Th1-and Th2-type cytokines regulate the expression and production of eotaxin and RANTES by human lung fibroblasts. Am J Respir Cell Mol Biol 1999, 20:777–786.

    PubMed  CAS  Google Scholar 

  73. Pepe C, Foley S, Shannon J, et al.: Differences in airway remodeling between subjects with severe and moderate asthma. J Allergy Clin Immunol 2005, 116:544–549.

    Article  PubMed  Google Scholar 

  74. Fryer AD, Stein LH, Nie Z, et al.: Neuronal eotaxin and the effects of ccr3 antagonist on airway hyperreactivity and M2 receptor dysfunction. J Clin Invest 2006, 116:228–236.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to James J. Lee PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jacobsen, E.A., Ochkur, S.I., Lee, N.A. et al. Eosinophils and asthma. Curr Allergy Asthma Rep 7, 18–26 (2007). https://doi.org/10.1007/s11882-007-0026-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-007-0026-y

Keywords

Navigation