Eosinophils are pleiotropic multi-functional leukocytes involved in initiation and propagation of diverse inflammatory responses. Recent studies examining eosinophil biology have focused on delineating the molecular basis of FIP1L1/PDGRFα-fusion gene induced HES, the molecular steps involved in eosinophil recruitment in tumor-associated eosinophilia and EGID, and the role of eosinophils in asthma. In this review, these studies are summarized, focusing on the implications of these findings in the understanding the role of eosinophils in diseases.

1.
Gleich GJ, Loegering DA: Immunobiology of eosinophils. Annu Rev Immunol 1984;2:429.
2.
Weller PF: Eosinophils: structure and functions. Curr Opin Immunol 1994;6:85.
3.
Rothenberg ME: Eosinophilia. N Engl J Med 1998;338:1592.
4.
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.
5.
Shi H: Eosinophils function as antigen-presenting cells. J Leukoc Biol 2004;76:520.
6.
Kita H: The eosinophil: a cytokine-producing cell? J Allergy Clin Immunol 1996;97:889.
7.
Gleich GJ, Adolphson CR: The eosinophilic leukocyte: structure and function. Adv Immunol 1986;39:177.
8.
Moser R, Fehr J, Bruijnzeel PL: IL-4 controls the selective endothelium-driven transmigration of eosinophils from allergic individuals. J Immunol 1992;149:1432.
9.
Sher A, Coffman RL, Hieny S, Cheever AW: Ablation of eosinophil and IgE responses with anti-IL-5 or anti-IL-4 antibodies fails to affect immunity against Schistosoma mansoni in the mouse. J Immunol 1990;145:3911.
10.
Horie S, Okubo Y, Hossain M, Sato E, Nomura H, Koyama S, Suzuki J, Isobe M, Sekiguchi M: Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis. Intern Med 1997;36:179.
11.
Bochner BS, Schleimer RP: The role of adhesion molecules in human eosinophil and basophil recruitment. J Allergy Clin Immunol 1994;94:427.
12.
Zimmermann N, Hershey GK, Foster PS, Rothenberg ME: Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol 2003;111:227.
13.
Zhu Z, Zheng T, Homer RJ, Kim YK, Chen NY, Cohn L, Hamid Q, Elias JA: Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation. Science 2004;304:1678.
14.
Rankin SM, Conroy DM, Williams TJ: Eotaxin and eosinophil recruitment: implications for human disease. Mol Med Today 2000;6:20.
15.
Collins PD, Marleau S, Griffiths-Johnson DA, Jose PJ, Williams TJ: Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 1995;182:1169.
16.
Flood-Page P, Phipps S, Menzies-Gow A, Ong YE, Kay AB: Effect of intravenous administration of an anti-IL-5 (mepolizumab) on allergen-induced tissue eosinophilia, the late-phase allergic reaction and the expression of a marker of repair/remodeling in human atopic subjects. J Allergy Clin Immunol 2003;111:S261.
17.
Hogan SP, Koskinen A, Foster PS: Interleukin-5 and eosinophils induce airway damage and bronchial hyperreactivity during allergic airway inflammation in BALB/c mice. Immunol Cell Biol 1997;75:284.
18.
Foster P, Hogan S, Ramsay A, Matthaei K, Young I: Interleukin-5 deficiency abolishes eosinophilia, airway hyperreactivity and lung damage in a mouse asthma model. J Exp Med 1996;183:195.
19.
Jose PJ, Griffiths-Johnson DA, Collins PD, Walsh DT, Moqbel R, Totty NF, Truong O, Hsuan JJ, Williams TJ: Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med 1994;179:881.
20.
Rothenberg ME, Luster AD, Lilly CM, Drazen JM, Leder P: Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung. J Exp Med 1995;181:1211.
21.
Zimmermann N, Hogan SP, Mishra A, Brandt EB, Bodette TR, Pope SM, Finkelman FD, Rothenberg ME: Murine eotaxin-2: a constitutive eosinophil chemokine induced by allergen challenge and IL-4 overexpression. J Immunol 2000;165:5839.
22.
Shinkai A, Yoshisue H, Koike M, Shoji E, Nakagawa S, Saito A, Takeda T, Imabeppu S, Kato Y, Hanai N, Anazawa H, Kuga T, Nishi T: A novel human CC chemokine, eotaxin-3, which is expressed in IL-4-stimulated vascular endothelial cells, exhibits potent activity toward eosinophils. J Immunol 1999;163:1602.
23.
Rothenberg ME, MacLean JA, Pearlman E, Luster AD, Leder P: Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. J Exp Med 1997;185:785.
24.
Pope SM, Fulkerson PC, Blanchard C, Akei HS, Nikolaidis NM, Zimmermann N, Molkentin JD, Rothenberg ME: Identification of a cooperative mechanism involving interleukin-13 and eotaxin-2 in experimental allergic lung inflammation. J Biol Chem 2005;280:13952.
25.
Gonzalo JA, Lloyd CM, Wen D, Albar JP, Wells TN, Proudfoot A, Martinez AC, Dorf M, Bjerke T, Coyle AJ, Gutierrez-Ramos JC: The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness. J Exp Med 1998;188:157.
26.
Murphy PM: The molecular biology of leukocyte chemoattractant receptors. Annu Rev Immunol 1994;12:593.
27.
Ponath PD, Qin S, Post TW, Wang J, Wu L, Gerard NP, Newman W, Gerard C, Mackay CR: Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med 1996;183:2437.
28.
Daugherty BL, Siciliano SJ, Demartino JA, Malkowitz L, Sirotina A, Springer MS: Cloning, expression, and characterization of the human eosinophil eotaxin receptor. J Exp Med 1996;183:2349.
29.
Humbles AA, Lu B, Friend DS, Okinaga S, Lora J, Al-Garawi A, Martin TR, Gerard NP, Gerard C: The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci USA 2002;99:1479.
30.
Ma W, Bryce PJ, Humbles AA, Laouini D, Yalcindag A, Alenius H, Friend DS, Oettgen HC, Gerard C, Geha RS: CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J Clin Invest 2002;109:621.
31.
Pope SM, Zimmermann N, Stringer KF, Karow ML, Rothenberg ME: The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. J Immunol 2005;175:5341.
32.
Tai PC, Hayes DJ, Clark JB, Spry CJF: Toxic effects of eosinophil secretion products on isolated rat heart cells in vitro. Biochem J 1982;204:75.
33.
Venge P, Dahl R, Hallgren R, Olsson I: Cationic proteins of human eosinophils and their role in the inflammatory reaction; in Mahmoud AAF, Austin KF (eds): The Eosinophil in Health and Disease. New York, Grune & Stratton, 1980, p 1131.
34.
Frigas E, Loegering DA, Gleich GJ: Cytotoxic effects of the guinea pig eosinophil major basic protein on tracheal epithelium. Lab Invest 1980;42:35.
35.
Gleich GJ, Frigas E, Loegering DA, Wassom DL, Steinmuller D: The cytotoxic properties of the eosinophil major basic protein. J Immunol 1979;123:2925.
36.
Young JD, Peterson CG, Venge P, Cohn ZA: Mechanism of membrane damage mediated by human eosinophil cationic protein. Nature 1986;321:613.
37.
Slifman NR, Loegering DA, McKean DJ, Gleich GJ: Ribonuclease activity associated with human eosinophil-derived neurotoxin and eosinophil cationic protein. J Immunol 1986;137:2913.
38.
Gleich GJ, Loegering DA, Bell MP, Checkel JL, Ackerman SJ, McKean DJ: Biochemical and functional similarities between human eosinophil-derived neurotoxin and eosinophil cationic protein: homology with ribonuclease. Proc Natl Acad Sci USA 1986;83:3146.
39.
Rosenberg HF, Domachowske JB: Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens. J Leukoc Biol 2001;70:691.
40.
Venge P, Bystrom J, Carlson M, Hakansson L, Karawacjzyk M, Peterson C, Seveus L, Trulson A: Eosinophil cationic protein (ECP): molecular and biological properties and the use of ECP as a marker of eosinophil activation in disease. Clin Exp Allergy 1999;29:1172.
41.
Zheutlin LM, Ackerman SJ, Gleich GJ, Thomas LL: Stimulation of basophil and rat mast cell histamine release by eosinophil granule-derived cationic proteins. J Immunol 1984;133:2180.
42.
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.
43.
Jacoby DB, Costello RM, Fryer AD: Eosinophil recruitment to the airway nerves. J Allergy Clin Immunol 2001;107:211.
44.
Morgan RK, Costello RW, Durcan N, Kingham PJ, Gleich GJ, McLean WG, Walsh MT: Diverse effects of eosinophil cationic granule proteins on IMR-32 nerve cell signalling and survival. Am J Respir Cell Mol Biol 2005;28:28.
45.
Mitra SN, Slungaard A, Hazen SL: Role of eosinophil peroxidase in the origins of protein oxidation in asthma. Redox Rep 2000;5:215.
46.
Wu W, Samoszuk MK, Comhair SA, Thomassen MJ, Farver CF, Dweik RA, Kavuru MS, Erzurum SC, Hazen SL: Eosinophils generate brominating oxidants in allergen-induced asthma. J Clin Invest 2000;105:1455.
47.
Wu W, Chen Y, Hazen SL: Eosinophil peroxidase, nitrates, protein tyrosyl residues. Implications for oxidative damage by nitrating intermediates in eosinophilic inflammatory disorders. J Biol Chem 1999;274:25933.
48.
MacPherson JC, Comhair SA, Erzurum SC, Klein DF, Lipscomb MF, Kavuru MS, Samoszuk MK, Hazen SL: Eosinophils are a major source of nitric oxide-derived oxidants in severe asthma: characterization of pathways available to eosinophils for generating reactive nitrogen species. J Immunol 2001;166:5763.
49.
Agosti JM, Altman LC, Ayars GH, Loegering DA, Gleich GJ, Klebanoff SJ: The injurious effect of eosinophil peroxidase, hydrogen peroxide, and halides on pneumocytes in vitro. J Allergy Clin Immunol 1987;79:496.
50.
Klion AD, Bochner BS, Gleich GJ, Nutman TB, Rothenberg ME, Simon HU, Wechsler ME, Weller PF, The Hypereosinophilic Syndromes Working Group: Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol 2006;117:1292.
51.
Stein M, Rothenberg ME: Hypereosinophilic syndromes and new therapeutic approaches including anti-IL-5. Expert Rev Clin Immunol 2006;1:633.
52.
Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, Griffin JD, Cross NC, Tefferi A, Malone J, Alam R, Schrier SL, Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, Kantarjian H, Marynen P, Coutre SE, Stone R, Gilliland DG: A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201.
53.
Yamada Y, Rothenberg ME, Cancelas JA: Current concepts on the pathogenesis of the Hypereosinophilic syndrome/chronic eosinophilic leukemia. Translational Oncogenomics 2006;2:1.
54.
La Starza R, Specchia G, Cuneo A, Beacci D, Nozzoli C, Luciano L, Aventin A, Sambani C, Testoni N, Foppoli M, Invernizzi R, Marynen P, Martelli MF, Mecucci C: The hypereosinophilic syndrome: fluorescence in situ hybridization detects the del(4)(q12)-FIP1L1/PDGFRA but not genomic rearrangements of other tyrosine kinases. Haematologica 2005;90:596.
55.
Vandenberghe P, Wlodarska I, Michaux L, Zachee P, Boogaerts M, Vanstraelen D, Herregods MC, Van Hoof A, Selleslag D, Roufosse F, Maerevoet M, Verhoef G, Cools J, Gilliland DG, Hagemeijer A, Marynen P: Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic leukemias. Leukemia 2004;18:734.
56.
Roche-Lestienne C, Lepers S, Soenen-Cornu V, Kahn JE, Lai JL, Hachulla E, Drupt F, Demarty AL, Roumier AS, Gardembas M, Dib M, Philippe N, Cambier N, Barete S, Libersa C, Bletry O, Hatron PY, Quesnel B, Rose C, Maloum K, Blanchet O, Fenaux P, Prin L, Preudhomme C: Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics. Leukemia 2005;19:792.
57.
Pardanani A, Ketterling RP, Brockman SR, Flynn HC, Paternoster SF, Shearer BM, Reeder TL, Li CY, Cross NC, Cools J, Gilliland DG, Dewald GW, Tefferi A: CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 2003;102:3093.
58.
Klion AD, Noel P, Akin C, Law MA, Gilliland DG, Cools J, Metcalfe DD, Nutman TB: Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness. Blood 2003;101:4660.
59.
Klion AD, Robyn J, Akin C, Noel P, Brown M, Law M, Metcalfe DD, Dunbar C, Nutman TB: Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome. Blood 2004;103:473.
60.
Cortes J, Ault P, Koller C, Thomas D, Ferrajoli A, Wierda W, Rios MB, Letvak L, Kaled ES, Kantarjian H: Efficacy of imatinib mesylate in the treatment of idiopathic hypereosinophilic syndrome. Blood 2003;101:4714.
61.
Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH: Treatment of hypereosinophilic syndrome with imatinib mesilate. Lancet 2002;359:1577.
62.
Daley GQ, Van Etten RA, Baltimore D: Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 1990;247:824.
63.
Stover EH, Chen J, Lee BH, Cools J, McDowell E, Adelsperger J, Cullen D, Coburn A, Moore SA, Okabe R, Fabbro D, Manley PW, Griffin JD, Gilliland DG: The small molecule tyrosine kinase inhibitor AMN107 inhibits TEL-PDGFRbeta and FIP1L1-PDGFRalpha in vitro and in vivo. Blood 2005;106:3206.
64.
Cools J, Stover EH, Boulton CL, Gotlib J, Legare RD, Amaral SM, Curley DP, Duclos N, Rowan R, Kutok JL, Lee BH, Williams IR, Coutre SE, Stone RM, DeAngelo DJ, Marynen P, Manley PW, Meyer T, Fabbro D, Neuberg D, Weisberg E, Griffin JD, Gilliland DG: PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFRalpha-induced myeloproliferative disease. Cancer Cell 2003;3:459.
65.
Pardanani A, Tefferi A: Imatinib therapy for hypereosinophilic syndrome and eosinophilia-associated myeloproliferative disorders. Leuk Res 2004;28(suppl 1):S47.
66.
Boyce JA, Friend D, Matsumoto R, Austen KF, Owen WF: Differentiation in vitro of hybrid eosinophil/basophil granulocytes: autocrine function of an eosinophil developmental intermediate. J Exp Med 1995;182:49.
67.
Nerlov C, McNagny KM, Doderlein G, Kowenz-Leutz E, Graf T: Distinct C/EBP functions are required for eosinophil lineage commitment and maturation. Genes Dev 1998;12:2413.
68.
Nerlov C, Graf T: PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev 1998;12:2403.
69.
McNagny KM, Sieweke MH, Doderlein G, Graf T, Nerlov C: Regulation of eosinophil-specific gene expression by a C/EBP-Ets complex and GATA-1. EMBO J 1998;17:3669.
70.
Lopez AF, Begley CG, Williamson DJ, Warren DJ, Vadas MA, Sanderson CJ: Murine eosinophil differentiation factor: an eosinophil-specific colony-stimulating factor with activity for human cells. J Exp Med 1986;163:1085.
71.
Rothenberg ME, Pomerantz JL, Owen WF, Avraham S, Soberman RJ, Austen KF, Stevens RL: Characterization of a human eosinophil proteoglycan, and augmentation of its biosynthesis and size by interleukin 3, interleukin 5, and granulocyte/macrophage colony stimulating factor. J Biol Chem 1988;263:13901.
72.
Lopez AF, Sanderson CJ, Gamble JR, Campbell HD, Young IG, Vadas MA: Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med 1988;167:219.
73.
Takatsu K, Takaki S, Hitoshi Y: Interleukin-5 and its receptor system: implications in the immune system and inflammation. Adv Immunol 1994;57:45.
74.
Serrano D, Ghiotto F, Roncella S, Airoldi I, Cutrona G, Truini M, Burgio VL, Baroni CD, Ferrarini M, Pistoia V: The patterns of IL2, IFN-gamma, IL4 and IL5 gene expression in Hodgkin’s disease and reactive lymph nodes are similar. Haematologica 1997;82:542.
75.
Di Biagio E, Sanchez-Borges M, Desenne JJ, Suarez-Chacon R, Somoza R, Acquatella G: Eosinophilia in Hodgkin’s disease: a role for interleukin 5. Int Arch Allergy Immunol 1996;110:244.
76.
Enokihara H, Koike T, Arimura H, Aoyagi M, Watanabe K, Nakamura Y, Yamashiro K, Tsuruoka N, Tsujimoto M, Saito K, et al: IL-5 mRNA expression in blood lymphocytes from patients with Kimura’s disease and parasite infection. Am J Hematol 1994;47:69.
77.
Kimura Y, Pawankar R, Aoki M, Niimi Y, Kawana S:Mast cells and T cells in Kimura’s disease express increased levels of interleukin-4, interleukin-5, eotaxin and RANTES. Clin Exp Allergy 2002;32:1787.
78.
Yamada Y, Rothenberg ME, Lee AW, Akei HS, Brandt EB, Williams DA, Cancelas JA: 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.
79.
Gotlib J, Cools J, Malone JM, 3rd, Schrier SL, Gilliland DG, Coutre SE: The FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. Blood 2004;103:2879.
80.
Elias JA, Lee CG, Zheng T, Ma B, Homer RJ, Zhu Z: New insights into the pathogenesis of asthma. J Clin Invest 2003;111:291.
81.
Busse W, lemanske R: Asthma. N Engl J Med 2001;344:350.
82.
Bandeira-Melo C, Bozza PT, Weller PF: The cellular biology of eosinophil eicosanoid formation and function. J Allergy Clin Immunol 2002;109:393.
83.
Lewis RA, Austen KF, Soberman RJ: Leukotrienes and other products of the 5-lipoxygenase pathway: biochemistry and relation to pathobiology in human diseases. N Engl J Med 1990;323:645.
84.
Nagata M, Saito K: The roles of cysteinyl leukotrienes in eosinophilic inflammation of asthmatic airways. Int Arch Allergy Immunol 2003;131(suppl 1):7.
85.
Busse WW: The role of leukotrienes in asthma and allergic rhinitis. Clin Exp Allergy 1996;26:868.
86.
Aalbers R, de Monchy JG: Cysteinyl-leukotriene receptor antagonist, bronchoconstriction, and airway hyperreactivity. Lancet 1991;338:445.
87.
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.
88.
Hamelmann E, Gelfand EW: IL-5-induced airway eosinophilia: the key to asthma? Immunol Rev 2001;179:182.
89.
Corry DB, Folkesson ML, Warnock DJ, Erle DJ, Matthay MA, Wiener-Kronish JP, Locksley RC: Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivy. J Exp Med 1996;183:109.
90.
Wills-Karp M: Immunologic basis of antigen-induced airway hyperresponsiveness. Ann Rev Immunol 1999;17:255–281.
91.
Webb DC, McKenzie AN, Matthaei KI, Rothenberg ME, Foster PS: Distinct spatial requirement for eosinophil-induced airways hyperreactivity. Immunol Cell Biol 2001;79:165.
92.
Leong KP, Huston DP: Understanding the pathogenesis of allergic asthma using mouse models. Ann Allergy Asthma Immunol 2001;87:96.
93.
Humbles AA, Lloyd CM, McMillan SJ, Friend DS, Xanthou G, McKenna EE, Ghiran S, Gerard NP, Yu C, Orkin SH, Gerard C: A critical role for eosinophils in allergic airways remodeling. Science 2004;305:1776.
94.
Lee JJ, Dimina D, Macias MP, Ochkur SI, McGarry MP, O’Neill KR, Protheroe C, Pero R, Nguyen T, Cormier SA, Lenkiewicz E, Colbert D, Rinaldi L, Ackerman SJ, Irvin CG, Lee NA: Defining a link with asthma in mice congenitally deficient in eosinophils. Science 2004;305:1773.
95.
Rothenberg ME, Hogan SP: The eosinophil. Annu Rev Immunol 2006;24:147.
96.
Wills-Karp M, Karp CL: Biomedicine. Eosinophils in asthma: remodeling a tangled tale. Science 2004;305:1726.
97.
Fulkerson P, Fischetti CA, McBride ML, Hassmann 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 USA 2006;103:16418.
98.
Young HW, Molina JG, Dimina D, Zhong H, Jacobson M, Chan LN, Chan TS, Lee JJ, Blackburn MR: A3 adenosine receptor signaling contributes to airway inflammation and mucus production in adenosine deaminase-deficient mice. J Immunol 2004;173:1380.
99.
Tager AM, Bromley SK, Medoff BD, Islam SA, Bercury SD, Friedrich EB, Carafone AD, Gerszten RE, Luster AD: Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol 2003;4:982.
100.
Terawaki K, Yokomizo T, Nagase T, Toda A, Taniguchi M, Hashizume K, Yagi T, Shimizu T: Absence of leukotriene B4 receptor 1 confers resistance to airway hyperresponsiveness and Th2-type immune responses. J Immunol 2005;175:4217.
101.
Swartz JM, Bystrom J, Dyer KD, Nitto T, Wynn TA, Rosenberg HF: Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes. J Leukoc Biol 2004;76:812.
102.
Voehringer D, Shinkai K, Locksley RM: Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity 2004;20:267.
103.
Gabazza EC, Taguchi O, Tamaki S, Takeya H, Kobayashi H, Yasui H, Kobayashi T, Hataji O, Urano H, Zhou H, Suzuki K, Adachi Y: Thrombin in the airways of asthmatic patients. Lung 1999;177:253.
104.
Mattes J, Yang M, Mahalingam S, Kuehr J, Webb DC, Simson L, Hogan SP, Koskinen A, McKenzie AN, Dent LA, Rothenberg ME, Matthaei KI, Young IG,. Foster PS: Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma. J Exp Med 2002;195:1433.
105.
Leckie MJ, ten Brinke A, Khan J, Diamant Z, O’Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ: Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000;356:2144.
106.
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.
107.
Flood-Page P, Menzies-Gow A, Phipps S, Compton C, Walls C, Barnes N, Robinson DS, Kay AB: Reduction of tissue eosinophils in mild atopic asthmatics by an anti-IL-5 monoclonal antibody (mepolizumab) is associated with inhibition of tenascin deposition within the bronchial epithelium basement membrane. Am J Respir Crit Care Med 2002;109:165.
108.
Phipps S, Flood-Page P, Menzies-Gow A, Wangoo A, Barnes NC, Barkans J, Robinson DS, Kay AB: Anti-IL-5 (mepolizumab) reduces the expression of tenascin, procollagen and lumican in the reticular basement membrane of human atopic asthmatics (abstract). J Allergy Clin Immunol 2003;111:S278.
109.
Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, Wardlaw AJ, Pavord ID: Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet 2002;360:1715.
110.
Silberstein DS: Eosinophil function in health and disease. Crit Rev Oncol Hematol 1995;19:47.
111.
Rothenberg ME, Mishra A, Brandt EB, Hogan SP: Gastrointestinal eosinophils in health and disease. Adv Immunol 2001;78:291.
112.
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.
113.
Matthews AN, Friend DS, Zimmermann N, Sarafi MN, Luster AD, Pearlman E, Wert SE, Rothenberg ME: Eotaxin is required for the baseline level of tissue eosinophils. Proc Natl Acad Sci USA 1998;95:6273.
114.
Mishra A, Hogan SP, Brandt EB, Wagner N, Crossman MW, Foster ME, Rothenberg PS: Enterocyte expression of the eotaxin and interleukin-5 transgenes induces compartmentalized dysregulation of eosinophil trafficking. J Biol Chem 2002;277:4406.
115.
Garcia-Zepeda EA, Rothenberg ME, Ownbey RT, Celestin J, Leder P, Luster AD: Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia. Nat Med 1996;2:449.
116.
Butt AM, Murch SH, Ng C-L, Kitching P, Montgomery SM, Phillips AD, Walker-Smith JA, Thomson MA: Upregulated eotaxin expression and T cell infiltration in the basal and papillary epithelium in cows milk associated reflux esophagitis. Arch Dis Child 2002;87:124.
117.
Mir A, Minguez M, Tatay J, Pascual I, Pena A, Sanchiz V, Almela P, Mora F, Benages A: Elevated serum eotaxin levels in patients with inflammatory bowel disease. Am J Gastroenterol 2002;97:1452.
118.
Jeziorska M, Haboubi N, Schofield P, Woolley DE: Distribution and activation of eosinophils in inflammatory bowel disease using an improved immunohistochemical technique. J Pathol 2001;194:484.
119.
Chen W, Paulus B, Shu D, Wilson, Chadwick V: Increased serum levels of eotaxin in patients with inflammatory bowel disease. Scand J Gastroenterol 2001;36:515.
120.
Kunkel EJ, Butcher EC: Chemokines and the tissue-specific migration of lymphocytes. Immunity 2002;16:1.
121.
Hogan SP, Rothenberg ME, Forbes E, Smart VE, Matthaei KI, Foster PS: Chemokines in eosinophil-associated gastrointestinal disorders. Curr Allergy Asthma Rep 2004;4:74.
122.
Weg VB, Williams TJ, Lobb RR, Nourshargh S: A monoclonal antibody recognizing very late activation antigen-4 inhibits eosinophil accumulation in vivo. J Exp Med 1993;177:561.
123.
Abraham WM, Sielczak MW, Ahmed A, Cortes A, Lauredo IT, Kim J, Pepinsky B, Benjamin CD, Leone DR, Lobb RR, et al: Alpha 4-integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep. J Clin Invest 1994;93:776.
124.
Pretolani M, Ruffie C, Lapa e Silva JR, Joseph D, Lobb RR, Vargaftig BB: Antibody to very late activation antigen 4 prevents antigen-induced bronchial hyperreactivity and cellular infiltration in the guinea pig airways. J Exp Med 1994;180:795.
125.
Nakajima H, Sano H, Nishimura T, Yoshida S, Iwamoto I: Role of vascular cell adhesion molecule 1/very late activation antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue. J Exp Med 1994;179:1145.
126.
Gonzalo JA, Lloyd CM, Kremer L, Finger E, Martinez AC, Siegelman MH, Cybulsky M, Gutierrez-Ramos JC: Eosinophil recruitment to the lung in a murine model of allergic inflammation: the role of T cells, chemokines, and adhesion receptors. J Clin Invest 1996;98:2332.
127.
Butcher EC, Williams M, Youngman K, Rott L, Briskin M: Lymphocyte trafficking and regional immunity. Adv Immunol 1999;72:209.
128.
Rothenberg ME, Mishra A, Brandt EB, Hogan SP: Gastrointestinal eosinophils. Immunol Rev 2001;179:139.
129.
Hogan SP, Mishra A, Brandt EB, Royalty MP, Pope SM, Zimmermann N, Foster PS, Rothenberg ME: A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat Immunol 2001;2:353.
130.
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 USA 2000;97:6681.
131.
Forbes E, Murase T, Yang M, Matthaei KI, Lee JJ, Lee NA, Foster PS, Hogan SP: Immunopathogenesis of experimental ulcerative colitis is mediated by eosinophil peroxidase. J Immunol 2004;172:5664.
132.
Forbes E, Hulett M, Ahrens R, Wagner N, Smart V, Matthaei KI, Brandt EB, Dent LA, Rothenberg ME, Tang M, Foster PS, Hogan SP: ICAM-1-dependent pathways regulate colonic eosinophilic inflammation. J Leukoc Biol 2006;26:26.
133.
Hohki G, Terada N, Hamano N, Kitaura M, Nakajima T, Yoshie O, Ikeda T, Kimura S, Konno A: The effects of eotaxin on the surface adhesion molecules of endothelial cells and on eosinophil adhesion to microvascular endothelial cells. Biochem Biophys Res Commun 1997;241:136.
134.
Weber C, Kitayama J, Springer TA: Differential regulation of B1 and B2 integrin avidity by chemoattractants in eosinophils. Proc Natl Acad Sci USA 1996;93:10939.
135.
Lowe D, Jorizzo J, Hutt MSR: Tumour-associated eosinophilia: a review. J Clin Pathol 1981;34:1343.
136.
Samoszuk MK: Eosinophils and human cancer. Histol Histopathol 1997;12:807.
137.
Ownby HE, Roi LD, Isenberg RR, Brennan MJ: Peripheral lymphocyte and eosinophil counts as indicators of prognosis in primary breast cancer. Cancer 1983;52:126.
138.
Goldsmith MM, Belchis DA, Cresson DH, Merritt, 3rd WD, Askin FB: The importance of the eosinophil in head and neck cancer. Otolaryngol Head Neck Surg 1992;106:27.
139.
Dalal BI, Das KC, Dutta TK, Malakar K: Local and systemic eosinophilia in patients with carcinoma of the uterine cervix undergoing radiation therapy: correlation with radiation response. Clin Oncol (R Coll Radiol) 1992;4:18.
140.
Bethwaite PB, Holloway LJ, Yeong ML, Thornton A: Effect of tumour associated tissue eosinophilia on survival of women with stage IB carcinoma of the uterine cervix. J Clin Pathol 1993;46:1016.
141.
Nielsen HJ, Hansen U, Christensen IJ, Reimert CM, Brunner N, Moesgaard F: Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue. J Pathol 1999;189:487.
142.
Tepper RI, Pattengale PK, Leder P: Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell 1989;57:503.
143.
Tepper RI: The eosinophil-mediated antitumor activity of interleukin-4. J Allergy Clin Immunol 1994;94:1225.
144.
Kruger-Krasagakes S, Li W, Richter G, Diamantstein T, Blankenstein T: Eosinophils infiltrating interleukin-5 gene-transfected tumors do not suppress tumor growth. Eur J Immunol 1993;23:992.
145.
Mattes J, Hulett M, Xie W, Hogan S, Rothenberg ME, Foster P, Parish C: Immunotherapy of cytotoxic T cell-resistant tumors by T helper 2 cells: an eotaxin and STAT6-dependent process. J Exp Med 2003;197:387.
146.
Cormier SA, Taranova AG, Bedient C, Nguyen T, Protheroe C, Pero R, Dimina D, Ochkur SI, O’Neill KO, Colbert D, Lombari TR, Constant S, McGarry MP, Lee JJ, Lee NA: Pivotal advance: eosinophil infiltration of solid tumors is an early and persistent inflammatory host response. J Leukoc Biol 2006;79:1131–1139.
147.
Tsopanoglou NE, Pipili-Synetos E, Maragoudakis ME: Leukotrienes C4 and D4 promote angiogenesis via a receptor-mediated interaction. Eur J Pharmacol 1994;258:151.
148.
Kanayasu T, Nakao-Hayashi J, Asuwa N, Morita I, Ishii T, Ito H, Murota S: Leukotriene C4 stimulates angiogenesis in bovine carotid artery endothelial cells in vitro. Biochem Biophys Res Commun 1989;159:572.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.