The Journal of Allergy and Clinical Immunology
Volume 126, Issue 1 , Pages 16-25 , July 2010

What targeting eosinophils has taught us about their role in diseases

  • Bruce S. Bochner, MD

      Affiliations

    • Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md
    • Corresponding Author InformationReprint requests: Bruce S. Bochner, MD, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224.
    • ,
  • Gerald J. Gleich, MD

      Affiliations

    • Departments of Dermatology, Medicine, and Pediatrics, Health Sciences Center, School of Medicine, University of Utah, Salt Lake City, Utah

Received 5 January 2010 ,Revised 8 February 2010 ,Accepted 9 February 2010.

References 

  1. Ehrlich P. Beiträge zur Kenntnis der granulierten Bindegewebszellen und der eosinophilen Leucocyten. Arch Anat Physiol. 1879;3:166–182
  2. Schlecht H, Schwenker G. Über die Beziehungen der Eosinophilie zur Anaphylaxie. Dtsch Arch Klin Med. 1912;108:405–428
  3. Samter M, Kofqed MA, Pieper W. A factor in lungs of anaphylactically shocked guinea pigs which can induce eosinophilia in normal animals. J Hematol. 1953;8:1078–1090
  4. Jose PJ, Griffiths-Johnson DA, Collins PD, Walsh DT, Moqbel R, Totty NF, et al. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med. 1994;179:881–887
  5. Goetzl E, Wasserman S, Austen K. Eosinophil polymorphonuclear leukocyte function in immediate hypersensitivity. Arch Pathol. 1975;99:1–4
  6. Gleich GJ, Olson GM, Loegering DA. The effect of ablation of eosinophils on immediate-type hypersensitivity reactions. Immunology. 1979;38:343–353
  7. Frigas E, Loegering DA, Solley GO, Farrow GM, Gleich GJ. Elevated levels of the eosinophil granule major basic protein in the sputum of patients with bronchial asthma. Proc Mayo Clin. 1981;56:345–353
  8. Filley WV, Holley KE, Kephart GM, Gleich GJ. Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma. Lancet. 1982;2:11–15
  9. Ayars GH, Altman LC, Gleich GJ, Loegering DA, Baker CB. Eosinophil- and eosinophil granule-mediated pneumocyte injury. J Allergy Clin Immunol. 1985;76:595–604
  10. Dor PJ, Ackerman SJ, Gleich GJ. Charcot-Leyden crystal protein and eosinophil granule major basic protein in sputum of patients with respiratory diseases. Am Rev Respir Dis. 1984;130:1072–1077
  11. Flavahan NA, Slifman NR, Gleich GJ, Vanhoutte PM. Human eosinophil major basic protein causes hyperreactivity of respiratory smooth muscle. Am Rev Respir Dis. 1988;138:685–688
  12. Lefort J, Nahori MA, Ruffie C, Vargaftig BB, Pretolani M. In vivo neutralization of eosinophil-derived major basic protein inhibits antigen-induced bronchial hyperreactivity in sensitized guinea pigs. J Clin Invest. 1996;97:1117–1121
  13. Gleich GJ, Hunt LW, Bochner BS, Schleimer RP. Glucocorticoid effects on human eosinophils. In:  Schleimer RP,  Busse WW,  O'Byrne P editor. Inhaled glucocorticoids in asthma: mechanisms and clinical actions. New York: Marcel Dekker, Inc; 1996;p. 279–308
  14. Campbell HD, Tucker WQJ, Hort Y, Martinson ME, Mayo G, Clutterbuck EJ, et al. Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5). Proc Natl Acad Sci U S A. 1987;84:6629–6633
  15. Clutterbuck E, Shields JG, Gordon J, Smith SH, Boyd A, Callard RE, et al. Recombinant human interleukin 5 is an eosinophil differentiation factor but has no activity in standard human B cell growth factor assays. Eur J Immunol. 1987;17:1743–1750
  16. Wise EL, Duchesnes C, da Fonseca PC, Allen RA, Williams TJ, Pease JE. Small molecule receptor agonists and antagonists of CCR3 provide insight into mechanisms of chemokine receptor activation. J Biol Chem. 2007;282:27935–27943
  17. Pease JE, Williams TJ. Chemokines and their receptors in allergic disease. J Allergy Clin Immunol. 2006;118:305–320
  18. Leckie MJ, Brinke A, Khan J, Diamant Z, O'Connor BJ, Walls CM, 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
  19. Kips JC, O'Connor BJ, Langley SJ, Woodcock A, Kerstjens HA, Postma DS, et al. Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med. 2003;167:1655–1659
  20. 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
  21. Flood-Page P, Menzies-Gow A, Phipps S, Ying S, Wangoo A, Ludwig MS, 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
  22. Flood-Page P, Swenson C, Faiferman I, Matthews J, Williams M, Brannick L, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007;176:1062–1071
  23. Bochner BS. Verdict in the case of therapies versus eosinophils: the jury is still out. J Allergy Clin Immunol. 2004;113:3–9
  24. Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360:973–984
  25. Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360:985–993
  26. Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008;358:1215–1228
  27. Dent LA, Strath M, Mellor AL, Sanderson CJ. Eosinophilia in transgenic mice expressing Interleukin-5. J Exp Med. 1990;172:1425–1431
  28. Tominaga A, Takaki S, Koyama N, Katoh S, Matsumoto R, Migita M, et al. Transgenic mice expressing a B-cell growth and differentiation factor gene (interleukin-5) develop eosinophilia and autoantibody production. J Exp Med. 1991;173:429–437
  29. Kopf M, Brombacher F, Hodgkin PD, Ramsay AJ, Milbourne EA, Dai WJ, et al. 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. 1996;4:15–24
  30. Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 1996;183:195–201
  31. Humbles AA, Lu B, Friend DS, Okinaga S, Lora J, Al-Garawi A, et al. The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci U S A. 2002;99:1479–1484
  32. Ma W, Bryce PJ, Humbles AA, Laouini D, Yalcindag A, Alenius H, et al. CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J Clin Invest. 2002;109:621–628
  33. Fulkerson PC, Fischetti CA, McBride ML, Hassman LM, Hogan SP, Rothenberg ME. A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation. Proc Natl Acad Sci U S A. 2006;103:16418–16423
  34. Fulkerson PC, Fischetti CA, Rothenberg ME. Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling. Am J Pathol. 2006;169:2117–2126
  35. Gurish MF, Humbles A, Tao H, Finkelstein S, Boyce JA, Gerard C, et al. CCR3 is required for tissue eosinophilia and larval cytotoxicity after infection with Trichinella spiralis. J Immunol. 2002;168:5730–5736
  36. Zhang M, Angata T, Cho JY, Miller M, Broide DH, Varki A. Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils. Blood. 2007;109:4280–4287
  37. Takatsu K, Nakajima H. IL-5 and eosinophilia. Curr Opin Immunol. 2008;20:288–294
  38. Asquith KL, Ramshaw HS, Hansbro PM, Beagley KW, Lopez AF, Foster PS. The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation. J Immunol. 2008;180:1199–1206
  39. Dyer KD, Moser JM, Czapiga M, Siegel SJ, Percopo CM, Rosenberg HF. Functionally competent eosinophils differentiated ex vivo in high purity from normal mouse bone marrow. J Immunol. 2008;181:4004–4009
  40. Bedi R, Du J, Sharma AK, Gomes I, Ackerman SJ. Human C/EBP-epsilon activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation. Blood. 2009;113:317–327
  41. Yamada T, Sun QY, Zeibecoglou K, Bungre J, North J, Kay AB, et al. IL-3, IL-5, granulocyte-macrophage colony-stimulating factor receptor alpha-subunit, and common beta-subunit expression by peripheral leukocytes and blood dendritic cells. J Allergy Clin Immunol. 1998;101:677–682
  42. Reed J, Kolbeck R, Molfino N, Kozhich A, Humbles A, Erjefalt J, et al. MEDI-563, a humanized anti-IL-5Rα antibody with enhanced effector function, induces reversible blood eosinopenia in mild asthmatics. [abstract] J Allergy Clin Immunol. 2008;121(suppl):S47
  43. Ackerman SJ, Bochner BS. Mechanisms of eosinophilia in the pathogenesis of hypereosinophilic disorders. Immunol Allergy Clin North Am. 2007;27:357–375
  44. Yamaguchi Y, Nishio H, Kishi K, Ackerman SJ, Suda T. C/EBPbeta and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter: implication for C/EBPbeta activity in eosinophil gene expression. Blood. 1999;94:1429–1439
  45. Hirasawa R, Shimizu R, Takahashi S, Osawa M, Takayanagi S, Kato Y, et al. Essential and instructive roles of GATA factors in eosinophil development. J Exp Med. 2002;195:1379–1386
  46. Yu C, Cantor AB, Yang H, Browne C, Wells RA, Fujiwara Y, et al. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med. 2002;195:1387–1395
  47. Yamanaka R, Barlow C, Lekstrom-Himes J, Castilla LH, Liu PP, Eckhaus M, et al. Impaired granulopoiesis, myelodysplasia, and early lethality in CCAAT/enhancer binding protein epsilon-deficient mice. Proc Natl Acad Sci U S A. 1997;94:13187–13192
  48. Du J, Stankiewicz MJ, Liu Y, Xi Q, Schmitz JE, Lekstrom-Himes JA, et al. Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein. J Biol Chem. 2002;277:43481–43494
  49. Lee JJ, Dimina D, Macias MP, Ochkur SI, McGarry MP, O'Neill KR, et al. Defining a link with asthma in mice congenitally deficient in eosinophils. Science. 2004;305:1773–1776
  50. Palframan RT, Collins PD, Severs NJ, Rothery S, Williams TJ, Rankin SM. Mechanisms of acute eosinophil mobilization from the bone marrow stimulated by interleukin 5: the role of specific adhesion molecules and phosphatidylinositol 3-kinase. J Exp Med. 1998;188:1621–1632
  51. Palframan RT, Collins PD, Williams TJ, Rankin SM. Eotaxin induces a rapid release of eosinophils and their progenitors from the bone marrow. Blood. 1998;91:2240–2248
  52. Voehringer D, van Rooijen N, Locksley RM. Eosinophils develop in distinct stages and are recruited to peripheral sites by alternatively activated macrophages. J Leukoc Biol. 2007;81:1434–1444
  53. Kay AB, Klion AD. Anti-interleukin-5 therapy for asthma and hypereosinophilic syndrome. Immunol Allergy Clin North Am. 2004;24:645–666
  54. Menzies-Gow A, Flood-Page P, Sehmi R, Burman J, Hamid Q, Robinson DS, et al. Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics. J Allergy Clin Immunol. 2003;111:714–719
  55. Bochner BS. Road signs guiding leukocytes along the inflammation superhighway. J Allergy Clin Immunol. 2000;106:817–828
  56. Rosenberg HF, Phipps S, Foster PS. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol. 2007;119:1303–1310
  57. Miller M, Sung KL, Muller WA, Cho JY, Roman M, Castaneda D, et al. Eosinophil tissue recruitment to sites of allergic inflammation in the lung is platelet endothelial cell adhesion molecule independent. J Immunol. 2001;167:2292–2297
  58. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006;24:147–174
  59. Myou S, Sano H, Fujimura M, Zhu X, Kurashima K, Kita T, et al. Blockade of eosinophil migration and airway hyperresponsiveness by cPLA2-inhibition. Nat Immunol. 2001;2:145–149
  60. Medoff BD, Seung E, Hong S, Thomas SY, Sandall BP, Duffield JS, et al. CD11b+ myeloid cells are the key mediators of Th2 cell homing into the airway in allergic inflammation. J Immunol. 2009;182:623–635
  61. Brandt EB, Zimmermann N, Muntel EE, Yamada Y, Pope SM, Mishra A, et al. The α4β7-integrin is dynamically expressed on murine eosinophils and involved in eosinophil trafficking to the intestine. Clin Exp Allergy. 2006;36:543–553
  62. Carlens J, Wahl B, Ballmaier M, Bulfone-Paus S, Forster R, Pabst O. Common gamma-chain-dependent signals confer selective survival of eosinophils in the murine small intestine. J Immunol. 2009;183:5600–5607
  63. Mishra A, Hogan SP, Lee JJ, Foster PS, Rothenberg ME. Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin Invest. 1999;103:1719–1727
  64. Mishra A, Hogan SP, Brandt EB, Wagner N, Crossman MW, Foster PS, et al. Enterocyte expression of the eotaxin and interleukin-5 transgenes induces compartmentalized dysregulation of eosinophil trafficking. J Biol Chem. 2002;277:4406–4412
  65. Zimmermann N, McBride ML, Yamada Y, Hudson SA, Jones C, Cromie KD, et al. Siglec-F antibody administration to mice selectively reduces blood and tissue eosinophils. Allergy. 2008;63:1156–1163
  66. Song DJ, Cho JY, Miller M, Strangman W, Zhang M, Varki A, et al. Anti-Siglec-F antibody inhibits oral egg allergen induced intestinal eosinophilic inflammation in a mouse model. Clin Immunol. 2009;131:157–169
  67. Song DJ, Cho JY, Lee SY, Miller M, Rosenthal P, Soroosh P, et al. Anti-Siglec-F antibody reduces allergen-induced eosinophilic inflammation and airway remodeling. J Immunol. 2009;183:5333–5341
  68. Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, 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
  69. Zheng T, Oh MH, Oh SY, Schroeder JT, Glick AB, Zhu Z. Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest Dermatol. 2009;129:742–751
  70. Hamelmann E, Cieslewicz G, Schwarze J, Ishizuka T, Joetham A, Heusser C, et al. Anti-interleukin 5 but not anti-IgE prevents airway inflammation and airway hyperresponsiveness. Am J Respir Crit Care Med. 1999;160:934–941
  71. Trifilieff A, Fujitani Y, Coyle AJ, Kopf M, Bertrand C. IL-5 deficiency abolishes aspects of airway remodelling in a murine model of lung inflammation. Clin Exp Allergy. 2001;31:934–942
  72. Cho JY, Miller M, Baek KJ, Han JW, Nayar J, Lee SY, et al. Inhibition of airway remodeling in IL-5-deficient mice. J Clin Invest. 2004;113:551–560
  73. Humbles AA, Lloyd CM, McMillan SJ, Friend DS, Xanthou G, McKenna EE, et al. A critical role for eosinophils in allergic airways remodeling. Science. 2004;305:1776–1779
  74. Broide DH. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling. J Allergy Clin Immunol. 2008;121:560–570
  75. Lee JJ, McGarry MP, Farmer SC, Denzler KL, Larson KA, Carrigan PE, 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
  76. Ochkur SI, Jacobsen EA, Protheroe CA, Biechele TL, Pero RS, McGarry MP, et al. Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model of respiratory inflammation with characteristics of severe asthma. J Immunol. 2007;178:7879–7889
  77. Shi HZ, Humbles A, Gerard C, Jin Z, Weller PF. Lymph node trafficking and antigen presentation by endobronchial eosinophils. J Clin Invest. 2000;105:945–953
  78. Shen HH, Ochkur SI, McGarry MP, Crosby JR, Hines EM, Borchers MT, et al. A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse. J Immunol. 2003;170:3296–3305
  79. Wang HB, Ghiran I, Matthaei K, Weller PF. Airway eosinophils: allergic inflammation recruited professional antigen-presenting cells. J Immunol. 2007;179:7585–7592
  80. Padigel UM, Hess JA, Lee JJ, Lok JB, Nolan TJ, Schad GA, et al. Eosinophils act as antigen-presenting cells to induce immunity to Strongyloides stercoralis in mice. J Infect Dis. 2007;196:1844–1851
  81. Jacobsen EA, Ochkur SI, Pero RS, Taranova AG, Protheroe CA, Colbert DC, et al. Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells. J Exp Med. 2008;205:699–710
  82. Akuthota P, Wang HB, Spencer LA, Weller PF. Immunoregulatory roles of eosinophils: a new look at a familiar cell. Clin Exp Allergy. 2008;38:1254–1263
  83. Aceves SS, Broide DH. Airway fibrosis and angiogenesis due to eosinophil trafficking in chronic asthma. Curr Mol Med. 2008;8:350–358
  84. Walsh ER, August A. Eosinophils and allergic airway disease: there is more to the story. Trends Immunol. 2010;31:39–44
  85. Phipps S, Flood-Page P, Menzies-Gow A, Ong YE, Kay AB. Intravenous anti-IL-5 monoclonal antibody reduces eosinophils and tenascin deposition in allergen-challenged human atopic skin. J Invest Dermatol. 2004;122:1406–1412
  86. Specht S, Saeftel M, Arndt M, Endl E, Dubben B, Lee NA, et al. Lack of eosinophil peroxidase or major basic protein impairs defense against murine filarial infection. Infect Immun. 2006;74:5236–5243
  87. Knott ML, Matthaei KI, Foster PS, Dent LA. The roles of eotaxin and the signal transducer and activator of transcription 6 signalling pathway in eosinophil recruitment and host resistance to the nematodes Nippostrongylus brasiliensis and Heligmosomoides bakeri. Mol Immunol. 2009;46:2714–2722
  88. Yousefi S, Gold JA, Andina N, Lee JJ, Kelly AM, Kozlowski E, et al. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med. 2008;14:949–953
  89. Linch SN, Kelly AM, Danielson ET, Pero R, Lee JJ, Gold JA. Mouse eosinophils possess potent antibacterial properties in vivo. Infect Immun. 2009;77:4976–4982
  90. Rosenberg HF, Domachowske JB. Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens. J Leukoc Biol. 2001;70:691–698
  91. Yamada Y, Rothenberg ME, Lee AW, Akei HS, Brandt EB, Williams DA, et al. The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease. Blood. 2006;107:4071–4079
  92. Forbes E, Murase T, Yang M, Matthaei KI, Lee JJ, Lee NA, et al. Immunopathogenesis of experimental ulcerative colitis is mediated by eosinophil peroxidase. J Immunol. 2004;172:5664–5675
  93. Hogan SP, Mishra A, Brandt EB, Foster PS, Rothenberg ME. A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy. Proc Natl Acad Sci U S A. 2000;97:6681–6686
  94. Hogan SP, Rosenberg HF, Moqbel R, Phipps S, Foster PS, Lacy P, et al. Eosinophils: biological properties and role in health and disease. Clin Exp Allergy. 2008;38:709–750
  95. Mishra A, Wang M, Pemmaraju VR, Collins MH, Fulkerson PC, Abonia JP, et al. Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology. 2008;134:204–214
  96. Boehme SA, Franz-Bacon K, Chen EP, Sasik R, Sprague LJ, Ly TW, et al. A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation. Int Immunol. 2009;21:81–93
  97. Matsuoka T, Hirata M, Tanaka H, Takahashi Y, Murata T, Kabashima K, et al. Prostaglandin D2 as a mediator of allergic asthma. Science. 2000;287:2013–2017
  98. Schratl P, Royer JF, Kostenis E, Ulven T, Sturm EM, Waldhoer M, et al. The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking. J Immunol. 2007;179:4792–4799
  99. Tager AM, Dufour JH, Goodarzi K, Bercury SD, von Andrian UH, Luster AD. BLTR mediates leukotriene B(4)-induced chemotaxis and adhesion and plays a dominant role in eosinophil accumulation in a murine model of peritonitis. J Exp Med. 2000;192:439–446
  100. Reese TA, Liang HE, Tager AM, Luster AD, Van Rooijen N, Voehringer D, et al. Chitin induces accumulation in tissue of innate immune cells associated with allergy. Nature. 2007;447:92–96
  101. Cho KJ, Seo JM, Shin Y, Yoo MH, Park CS, Lee SH, et al. Blockade of airway inflammation and hyperresponsiveness by inhibition of BLT2, a low-affinity leukotriene B4 receptor. Am J Respir Cell Mol Biol. 2010;42:294–303
  102. Miyahara N, Ohnishi H, Miyahara S, Takeda K, Matsubara S, Matsuda H, et al. Leukotriene B4 release from mast cells in IgE-mediated airway hyperresponsiveness and inflammation. Am J Respir Cell Mol Biol. 2009;40:672–682
  103. Cowden JM, Zhang M, Dunford PJ, Thurmond RL. The histamine H(4) receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. J Invest Dermatol. 2009;[Epub ahead of print]
  104. Thurmond RL, Gelfand EW, Dunford PJ. The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov. 2008;7:41–53
  105. Wong CK, Hu S, Cheung PF, Lam CW. TSLP induces chemotactic and pro-survival effects in eosinophils: implications in allergic inflammation. Am J Respir Cell Mol Biol. 2009;[Epub ahead of print]
  106. Garrett JK, Jameson SC, Thomson B, Collins MH, Wagoner LE, Freese DK, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004;113:115–119
  107. Plotz SG, Simon HU, Darsow U, Simon D, Vassina E, Yousefi S, et al. Use of an anti-interleukin-5 antibody in the hypereosinophilic syndrome with eosinophilic dermatitis. N Engl J Med. 2003;349:2334–2339
  108. Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002;360:1715–1721
  109. Wenzel SE. Eosinophils in asthma—closing the loop or opening the door?. N Engl J Med. 2009;360:1026–1028
  110. Gleich GJ. Anti-interleukin-5 therapy and severe asthma. N Engl J Med. 2009;360:2577
  111. Kim YJ, Prussin C, Martin B, Law MA, Haverty TP, Nutman TB, et al. Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti-IL-5 antibody SCH55700. J Allergy Clin Immunol. 2004;114:1449–1455
  112. Stein ML, Collins MH, Villanueva JM, Kushner JP, Putnam PE, Buckmeier BK, et al. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol. 2006;118:1312–1319
  113. Gevaert P, Lang-Loidolt D, Lackner A, Stammberger H, Staudinger H, Van Zele T, et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol. 2006;118:1133–1141
  114. Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010;59:21–30
  115. Simon D, Wardlaw A, Rothenberg ME. Organ-specific eosinophilic disorders of the skin, lung and gastrointestinal tract. J Allergy Clin Immunol. 2010;In press
  116. Stein ML, Villanueva JM, Buckmeier BK, Yamada Y, Filipovich AH, Assa'ad AH, et al. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol. 2008;121:1473–1483
  117. Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009;124:1319–1325
  118. Boucher RM, Gilbert-McClain L, Chowdhury B. Hypereosinophilic syndrome and mepolizumab. N Engl J Med. 2008;358:2838–2840
  119. Walsh GM. Reslizumab, a humanized anti-IL-5 mAb for the treatment of eosinophil-mediated inflammatory conditions. Curr Opin Mol Ther. 2009;11:329–336
  120. Kahn JE, Grandpeix-Guyodo C, Marroun I, Catherinot E, Mellot F, Roufosse F, et al. Sustained response to mepolizumab in refractory Churg-Strauss syndrome. J Allergy Clin Immunol. 2010;125:267–270
  121. Kim S, Israel E, Oren E, Wechsler M. Mepolizumab as a steroid-sparing treatment in the Churg Strauss syndrome. [abstract] Am J Respir Crit Care Med. 2009;179:A5368

 Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD

 Supported in part by grant AI072265 from the National Institutes of Health. Dr Bochner also received support for human immunology research from the Dana Foundation and as a Cosner Scholar in Translational Research from the Johns Hopkins University.

 Terms in boldface and italics are defined in the glossary on page 17.

PII: S0091-6749(10)00389-1

doi: 10.1016/j.jaci.2010.02.026

The Journal of Allergy and Clinical Immunology
Volume 126, Issue 1 , Pages 16-25 , July 2010

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