Advertisement

Eosinophile Granulozyten – Physiologie und Pathophysiologie

  • C. Sokollik
  • H.-U. SimonEmail author
Leitthema
  • 92 Downloads

Zusammenfassung

Die eosinophilen Granulozyten sind als Untergruppe der Leukozyten ein Teil des angeborenen Immunzellpools. Zusätzlich nehmen sie homöostatische Aufgaben im Gewebe war. Klassischerweise werden Allergien und Parasiteninfektionen mit einer erhöhten Eosinophilenzahl assoziiert, doch findet man eine Eosinophilie auch bei Vaskulitiden und Tumorerkrankungen. Die wichtigsten Steuerungselemente der Eosinophilen sind das Zytokin Interleukin 5 und die Eotaxine. Selbst produzieren Eosinophile die unterschiedlichsten Kommunikationsfaktoren und toxischen Proteine, die in den zytoplasmatischen Granula gespeichert sind und bei Bedarf abhängig vom jeweiligen Stimulus gezielt und schnell ausgeschüttet werden können. Zur Pathogenbekämpfung können Eosinophile auch extrazelluläre mitochondriale DNA-Netze herauskatapultieren. In dieser Übersicht werden Grundaufbau, Steuerung und Funktion der Eosinophilen im Gesunden und bei Krankheiten besprochen.

Schlüsselwörter

Interleukin 5 Eotaxin Zytoplasmatische Granula Antieosinophile Therapie Extrazelluläre DNA-Netze 

Eosinophilic granulocytes—Physiology and pathophysiology

Abstract

Eosinophilic granulocytes are a subpopulation of leucocytes and part of the innate immune cell pool. Additionally, they have homeostatic functions in different tissues. Classically, an increased number of eosinophils is associated with allergies and parasitic infections; however, eosinophilia can also be found in vasculitides and malignant tumors. The most important controlling factors of eosinophils are the cytokine interleukin 5 and eotaxins. Eosinophils are able to produce a broad range of signalling factors and toxic proteins, which are stored in cytoplasmic granules and can be quickly and specifically released when needed depending on the stimulus. To combat pathogens, eosinophils can catapult extracellular traps consisting of mitochondrial DNA and toxic proteins into the intercellular space. This review focuses on the basic structure, control and function of eosinophils in health and disease.

Keywords

Interleukin-5 Eotaxin Cytoplasmatic granules Anti-eosinophil therapy Extracellular traps 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

C. Sokollik und H.-U. Simon geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Ackerman SJ, Liu L, Kwatia MA et al (2002) Charcot-Leyden crystal protein (galectin-10) is not a dual function galectin with lysophospholipase activity but binds a lysophospholipase inhibitor in a novel structural fashion. J Biol Chem 277:14859–14868CrossRefGoogle Scholar
  2. 2.
    Arnold IC, Artola-Boran M, Tallon De Lara P et al (2018) Eosinophils suppress Th1 responses and restrict bacterially induced gastrointestinal inflammation. J Exp Med 215:2055–2072CrossRefGoogle Scholar
  3. 3.
    Beck LA, Thaci D, Hamilton JD et al (2014) Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 371:130–139CrossRefGoogle Scholar
  4. 4.
    Blanchard C, Simon D, Schoepfer A et al (2017) Eosinophilic esophagitis: unclear roles of IgE and eosinophils. J Intern Med 281:448–457CrossRefGoogle Scholar
  5. 5.
    Carretero R, Sektioglu IM, Garbi N et al (2015) Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat Immunol 16:609–617CrossRefGoogle Scholar
  6. 6.
    Chu VT, Beller A, Rausch S et al (2014) Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis. Immunity 40:582–593CrossRefGoogle Scholar
  7. 7.
    Chu VT, Frohlich A, Steinhauser G et al (2011) Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat Immunol 12:151–159CrossRefGoogle Scholar
  8. 8.
    Chua JC, Douglass JA, Gillman A et al (2012) Galectin-10, a potential biomarker of eosinophilic airway inflammation. PLoS ONE 7:e42549CrossRefGoogle Scholar
  9. 9.
    Cowardin CA, Buonomo EL, Saleh MM et al (2016) The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia. Nat Microbiol 1:16108CrossRefGoogle Scholar
  10. 10.
    Cross NC, Reiter A (2008) Fibroblast growth factor receptor and platelet-derived growth factor receptor abnormalities in eosinophilic myeloproliferative disorders. Acta Haematol 119:199–206CrossRefGoogle Scholar
  11. 11.
    Elishmereni M, Alenius HT, Bradding P et al (2011) Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro. Allergy 66:376–385CrossRefGoogle Scholar
  12. 12.
    Fabre V, Beiting DP, Bliss SK et al (2009) Eosinophil deficiency compromises parasite survival in chronic nematode infection. J Immunol 182(0):1577–1583CrossRefGoogle Scholar
  13. 13.
    Farhan RK, Vickers MA, Ghaemmaghami AM et al (2016) Effective antigen presentation to helper T cells by human eosinophils. Immunology 149:413–422CrossRefGoogle Scholar
  14. 14.
    Forbes E, Hulett M, Ahrens R et al (2006) ICAM-1-dependent pathways regulate colonic eosinophilic inflammation. J Leukoc Biol 80:330–341CrossRefGoogle Scholar
  15. 15.
    Furuta GT, Kagalwalla AF, Lee JJ et al (2013) The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut 62:1395–1405CrossRefGoogle Scholar
  16. 16.
    Gleich GJ, Klion AD, Lee JJ et al (2013) The consequences of not having eosinophils. Arerugi 68:829–835Google Scholar
  17. 17.
    Goh YP, Henderson NC, Heredia JE et al (2013) Eosinophils secrete IL-4 to facilitate liver regeneration. Proc Natl Acad Sci USA 110:9914–9919CrossRefGoogle Scholar
  18. 18.
    Gouon-Evans V, Pollard JW (2001) Eotaxin is required for eosinophil homing into the stroma of the pubertal and cycling uterus. Endocrinology 142:4515–4521CrossRefGoogle Scholar
  19. 19.
    Gouon-Evans V, Rothenberg ME, Pollard JW (2000) Postnatal mammary gland development requires macrophages and eosinophils. Development 127:2269–2282PubMedGoogle Scholar
  20. 20.
    Haldar P, Brightling CE, Hargadon B et al (2009) Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 360:973–984CrossRefGoogle Scholar
  21. 21.
    Heredia JE, Mukundan L, Chen FM et al (2013) Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration. Cell 153:376–388CrossRefGoogle Scholar
  22. 22.
    Hogan SP, Rosenberg HF, Moqbel R et al (2008) Eosinophils: biological properties and role in health and disease. Clin Exp Allergy 38:709–750CrossRefGoogle Scholar
  23. 23.
    Jacobsen EA, Zellner KR, Colbert D et al (2011) Eosinophils regulate dendritic cells and Th2 pulmonary immune responses following allergen provocation. J Immunol 187:6059–6068CrossRefGoogle Scholar
  24. 24.
    Jung Y, Wen T, Mingler MK et al (2015) IL-1beta in eosinophil-mediated small intestinal homeostasis and IgA production. Mucosal Immunol 8:930–942CrossRefGoogle Scholar
  25. 25.
    Kim HJ, Alonzo ES, Dorothee G et al (2010) Selective depletion of eosinophils or neutrophils in mice impacts the efficiency of apoptotic cell clearance in the thymus. PLoS ONE 5:e11439CrossRefGoogle Scholar
  26. 26.
    Kopf M, Brombacher F, Hodgkin PD et al (1996) IL-5-deficient mice have a developmental defect in CD5+ B‑1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity 4:15–24CrossRefGoogle Scholar
  27. 27.
    Lampinen M, Ronnblom A, Amin K et al (2005) Eosinophil granulocytes are activated during the remission phase of ulcerative colitis. Gut 54:1714–1720CrossRefGoogle Scholar
  28. 28.
    Melo RC, Liu L, Xenakis JJ et al (2013) Eosinophil-derived cytokines in health and disease: unraveling novel mechanisms of selective secretion. Allergy 68:274–284CrossRefGoogle Scholar
  29. 29.
    Melo RC, Weller PF (2010) Piecemeal degranulation in human eosinophils: a distinct secretion mechanism underlying inflammatory responses. Histol Histopathol 25:1341–1354PubMedPubMedCentralGoogle Scholar
  30. 30.
    Nussbaum JC, Van Dyken SJ, Von Moltke J et al (2013) Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 502:245–248CrossRefGoogle Scholar
  31. 31.
    Pepper RJ, Fabre MA, Pavesio C et al (2008) Rituximab is effective in the treatment of refractory Churg-Strauss syndrome and is associated with diminished T‑cell interleukin-5 production. Rheumatology (Oxf) 47:1104–1105CrossRefGoogle Scholar
  32. 32.
    Phipps S, Lam CE, Mahalingam S et al (2007) Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood 110:1578–1586CrossRefGoogle Scholar
  33. 33.
    Plaut M, Pierce JH, Watson CJ et al (1989) Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. Nature 339:64–67CrossRefGoogle Scholar
  34. 34.
    Qiu Y, Nguyen KD, Odegaard JI et al (2014) Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157:1292–1308CrossRefGoogle Scholar
  35. 35.
    Radonjic-Hoesli S, Valent P, Klion AD et al (2015) Novel targeted therapies for eosinophil-associated diseases and allergy. Annu Rev Pharmacol Toxicol 55:633–656CrossRefGoogle Scholar
  36. 36.
    Rosenberg HF, Dyer KD, Foster PS (2013) Eosinophils: changing perspectives in health and disease. Nat Rev Immunol 13:9–22CrossRefGoogle Scholar
  37. 37.
    Schrezenmeier H, Thome SD, Tewald F et al (1993) Interleukin-5 is the predominant eosinophilopoietin produced by cloned T lymphocytes in hypereosinophilic syndrome. Exp Hematol 21:358–365PubMedGoogle Scholar
  38. 38.
    Shi HZ, Xiao CQ, Li CQ et al (2004) Endobronchial eosinophils preferentially stimulate T helper cell type 2 responses. Allergy 59:428–435CrossRefGoogle Scholar
  39. 39.
    Simon D, Simon HU, Yousefi S (2013) Extracellular DNA traps in allergic, infectious, and autoimmune diseases. Allergy 68:409–416CrossRefGoogle Scholar
  40. 40.
    Simon HU, Plotz SG, Dummer R et al (1999) Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med 341:1112–1120CrossRefGoogle Scholar
  41. 41.
    Simon HU, Yousefi S, Schranz C et al (1997) Direct demonstration of delayed eosinophil apoptosis as a mechanism causing tissue eosinophilia. J Immunol 158:3902–3908PubMedGoogle Scholar
  42. 42.
    Soragni A, Yousefi S, Stoeckle C et al (2015) Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation. Mol Cell 57:1011–1021CrossRefGoogle Scholar
  43. 43.
    Spencer LA, Melo RC, Perez SA et al (2006) Cytokine receptor-mediated trafficking of preformed IL-4 in eosinophils identifies an innate immune mechanism of cytokine secretion. Proc Natl Acad Sci USA 103:3333–3338CrossRefGoogle Scholar
  44. 44.
    Stahle-Backdahl M, Maim J, Veress B et al (2000) Increased presence of eosinophilic granulocytes expressing transforming growth factor-beta1 in collagenous colitis. Scand J Gastroenterol 35:742–746CrossRefGoogle Scholar
  45. 45.
    Steinbach KH, Schick P, Trepel F et al (1979) Estimation of kinetic parameters of neutrophilic, eosinophilic, and basophilic granulocytes in human blood. Blut 39:27–38CrossRefGoogle Scholar
  46. 46.
    Stoeckle C, Geering B, Yousefi S et al (2016) RhoH is a negative regulator of eosinophilopoiesis. Cell Death Differ 23:1961–1972CrossRefGoogle Scholar
  47. 47.
    Straumann A, Conus S, Grzonka P et al (2010) Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 59:21–30CrossRefGoogle Scholar
  48. 48.
    Valent P, Klion AD, Horny HP et al (2012) Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol 130:607–612.e9CrossRefGoogle Scholar
  49. 49.
    Von Gunten S, Vogel M, Schaub A et al (2007) Intravenous immunoglobulin preparations contain anti-Siglec-8 autoantibodies. J Allergy Clin Immunol 119:1005–1011CrossRefGoogle Scholar
  50. 50.
    Wang HB, Ghiran I, Matthaei K et al (2007) Airway eosinophils: allergic inflammation recruited professional antigen-presenting cells. J Immunol 179:7585–7592CrossRefGoogle Scholar
  51. 51.
    Wu D, Molofsky AB, Liang HE et al (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243–247CrossRefGoogle Scholar
  52. 52.
    Yousefi S, Gold JA, Andina N et al (2008) Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med 14:949–953CrossRefGoogle Scholar
  53. 53.
    Yousefi S, Sharma SK, Stojkov D et al (2018) Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation. J Leukoc Biol 104:205–214CrossRefGoogle Scholar
  54. 54.
    Zhang X, Cheng E, Huo X et al (2012) Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells. PLoS ONE 7:e50037CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Pädiatrische Gastroenterologie, Hepatologie und ErnährungKinderklinik, Inselspital, Universität BernBernSchweiz
  2. 2.Institut für PharmakologieUniversität Bern, Inselspital, INO-FBernSchweiz

Personalised recommendations