Mechanisms of Eosinophilia in the Pathogenesis of Hypereosinophilic Disorders

Kay, 2005, The role of eosinophils in the pathogenesis of asthma, Trends Mol Med, 11, 148, 10.1016/j.molmed.2005.02.002 Kay, 2004, A role for eosinophils in airway remodelling in asthma, Trends Immunol, 25, 477, 10.1016/j.it.2004.07.006 Gomes, 2005, Eosinophil-fibroblast interactions induce fibroblast IL-6 secretion and extracellular matrix gene expression: implications in fibrogenesis, J Allergy Clin Immunol, 116, 796, 10.1016/j.jaci.2005.06.031 Lee, 2004, Defining a link with asthma in mice congenitally deficient in eosinophils, Science, 305, 1773, 10.1126/science.1099472 Humbles, 2004, A critical role for eosinophils in allergic airways remodeling, Science, 305, 1776, 10.1126/science.1100283 Phipps, 2004, Intravenous anti-IL-5 monoclonal antibody reduces eosinophils and tenascin deposition in allergen-challenged human atopic skin, J Invest Dermatol, 122, 1406, 10.1111/j.0022-202X.2004.22619.x Flood-Page, 2003, Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics, J Clin Invest, 112, 1029, 10.1172/JCI17974 Stein, 2006, Anti-IL-5 (Mepolizumab) therapy for eosinophilic esophagitis, J Allergy Clin Immunol, 118, 1312, 10.1016/j.jaci.2006.09.007 Rothenberg, 2006, Steroid-sparing effects of anti-IL-5 monoclonal antibody (Mepolizumab) therapy in patients with HES: a multicenter, randomized, double-blind, placebo-controlled trial, Blood [ASH Annual Meeting Abstracts], 108, 373 Takatsu, 1988, T cell-replacing factor (TRF)/interleukin 5 (IL-5): molecular and functional properties, Immunol Rev, 102, 107, 10.1111/j.1600-065X.1988.tb00743.x Plaut, 1989, Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores, Nature, 339, 64, 10.1038/339064a0 Galli, 1994, Mast cell and eosinophil cytokines in allergy and inflammation, vol. 2, 255 Palacios, 1987, Ly1+ PRO-B lymphocyte clones. Phenotype, growth requirements and differentiation in vitro and in vivo, EMBO J, 6, 3687, 10.1002/j.1460-2075.1987.tb02702.x Takatsu, 1989, Signal transduction through interleukin-5 receptors, Cold Spring Harb Symp Quant Biol, 2, 745, 10.1101/SQB.1989.054.01.088 Yamaguchi, 1988, Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors, J Exp Med, 167, 43, 10.1084/jem.167.1.43 Sanderson, 1990, Eosinophil differentiation factor (interleukin-5), Immunol Ser, 49, 231 Sanderson, 1991, Control of eosinophilia, Int Arch Allergy Appl Immunol, 94, 122, 10.1159/000235342 Owen, 1989, Interleukin 5 and phenotypically altered eosinophils in the blood of patients with the idiopathic hypereosinophilic syndrome, J Exp Med, 170, 343, 10.1084/jem.170.1.343 Owen, 1990, Hypodense eosinophils and interleukin 5 activity in the blood of patients with the eosinophilia-myalgia syndrome, Proc Natl Acad Sci U S A, 87, 8647, 10.1073/pnas.87.21.8647 Sanderson, 1992, Interleukin-5, eosinophils, and disease, Blood, 79, 3101, 10.1182/blood.V79.12.3101.bloodjournal79123101 Dent, 1990, Eosinophilia in transgenic mice expressing Interleukin-5, J Exp Med, 172, 1425, 10.1084/jem.172.5.1425 Tominaga, 1991, Transgenic mice expressing a B-cell growth and differentiation factor gene (interleukin-5) develop eosinophilia and autoantibody production, J Exp Med, 173, 429, 10.1084/jem.173.2.429 Kopf, 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, 10.1016/S1074-7613(00)80294-0 Foster, 1996, Interleukin 5 deficiency abolishes airways eosinophilia, airways hyperreactivity, and lung damage in mouse asthma model, J Exp Med, 183, 195, 10.1084/jem.183.1.195 Cho, 2004, Inhibition of airway remodeling in IL-5-deficient mice, J Clin Invest, 113, 551, 10.1172/JCI19133 Cantor, 2001, Hematopoietic development: a balancing act, Curr Opin Genet Dev, 11, 513, 10.1016/S0959-437X(00)00226-4 Miyamoto, 2005, Lineage promiscuous expression of transcription factors in normal hematopoiesis, Int J Hematol, 81, 361, 10.1532/IJH97.05003 Akashi, 2005, Lineage promiscuity and plasticity in hematopoietic development, Ann N Y Acad Sci, 1044, 125, 10.1196/annals.1349.016 McNagny, 2002, Making eosinophils through subtle shifts in transcription factor expression, J Exp Med, 195, F43, 10.1084/jem.20020636 Yamaguchi, 1999, 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, 94, 1429, 10.1182/blood.V94.4.1429 Querfurth, 2000, Antagonism between C/EBPbeta and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors, Genes Dev, 14, 2515, 10.1101/gad.177200 Hirasawa, 2002, Essential and instructive roles of GATA factors in eosinophil development, J Exp Med, 195, 1379, 10.1084/jem.20020170 Yu, 2002, 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, 195, 1387, 10.1084/jem.20020656 Du, 2002, 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, 277, 43481, 10.1074/jbc.M204777200 Zimmermann, 2005, Analysis of the CCR3 promoter reveals a regulatory region in exon 1 that binds GATA-1, BMC Immunol, 6, 7, 10.1186/1471-2172-6-7 Stopka, 2005, PU.1 inhibits the erythroid program by binding to GATA-1 on DNA and creating a repressive chromatin structure, EMBO J, 24, 3712, 10.1038/sj.emboj.7600834 Du J, Vyas D, Xi Q, et al. Double GAT-1 binding sites Specify PU.1 and GATA-1 synergy in transcriptional regulation of myeloid lineage-specific genes. Nucleic Acids Research 2007; submitted for publication. Zhang, 1997, Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha- deficient mice, Proc Natl Acad Sci U S A, 94, 569, 10.1073/pnas.94.2.569 Ackerman, 2000, Eosinophilopoiesis: to be or not to be (an eosinophil)? That is the question: transcriptional themes regulating eosinophil genes and development, Respir Med, 94, 1135, 10.1053/rmed.2000.0913 Du, 2007, Impaired eosinophilopoiesis and eosinophil gene expression in PU.1 (Spi-1 oncogene) deficient mice, Exp Hematol Yamanaka, 1997, Impaired granulopoiesis, myelodysplasia, and early lethality in CCAAT/enhancer binding protein epsilon-deficient mice, Proc Natl Acad Sci U S A, 94, 13187, 10.1073/pnas.94.24.13187 Yamanaka, 1998, CCAAT/enhancer binding proteins are critical components of the transcriptional regulation of hematopoiesis, Int J Mol Med, 1, 213 Rosenberg, 1993, Neutrophil-specific granule deficiency includes eosinophils, Blood, 82, 268, 10.1182/blood.V82.1.268.bloodjournal821268 Klion, 2004, Safety and efficacy of the monoclonal anti-interleukin-5 antibody SCH55700 in the treatment of patients with hypereosinophilic syndrome, Blood, 103, 2939, 10.1182/blood-2003-10-3620 Menzies-Gow, 2003, 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, 111, 714, 10.1067/mai.2003.1382 Clutterbuck, 1989, Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF, Blood, 73, 1504, 10.1182/blood.V73.6.1504.1504 Seminario, 1999, Intracellular expression and release of FceRIa by human eosinophils, J Immunol, 162, 6893, 10.4049/jimmunol.162.11.6893 Smith, 2000, Blood eosinophils from atopic donors express messenger RNA for the alpha, beta, and gamma subunits of the high-affinity IgE receptor (Fc epsilon RI) and intracellular, but not cell surface, alpha subunit protein, J Allergy Clin Immunol, 105, 309, 10.1016/S0091-6749(00)90081-2 Ackerman, 1983, Localization of eosinophil granule major basic protein in human basophils, J Exp Med, 158, 946, 10.1084/jem.158.3.946 Ackerman, 1982, Formation of Charcot-Leyden crystals by human basophils, J Exp Med, 155, 1597, 10.1084/jem.155.6.1597 Abu-Ghazaleh, 1992, Eosinophil granule proteins in peripheral blood granulocytes, J Leukoc Biol, 52, 611, 10.1002/jlb.52.6.611 Bochner, 2001, Mast cells, basophils, and eosinophils: distinct but overlapping pathways for recruitment, Immunol Rev, 179, 5, 10.1034/j.1600-065X.2001.790101.x Voehringer, 2007, Eosinophils develop in distinct stages and are recruited to peripheral sites by alternatively activated macrophages, J Leukoc Biol, 81, 1434, 10.1189/jlb.1106686 Aizawa, 2003, Molecular analysis of human Siglec-8 orthologs relevant to mouse eosinophils: identification of mouse orthologs of Siglec-5 (mSiglec-F) and Siglec-10 (mSiglec-G), Genomics, 82, 521, 10.1016/S0888-7543(03)00171-X Zhang, 2004, The murine inhibitory receptor mSiglec-E is expressed broadly on cells of the innate immune system whereas mSiglec-F is restricted to eosinophils, Eur J Immunol, 34, 1175, 10.1002/eji.200324723 Kikly, 2000, Identification of SAF-2, a novel Siglec expressed on eosinophils, mast cells and basophils, J Allergy Clin Immunol, 105, 1093, 10.1067/mai.2000.107127 Palframan, 1998, 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, 188, 1621, 10.1084/jem.188.9.1621 Palframan, 1998, Eotaxin induces a rapid release of eosinophils and their progenitors from the bone marrow, Blood, 91, 2240, 10.1182/blood.V91.7.2240 Werfel, 1996, Functional regulation of b1 integrins and human eosinophils by divalent cations and cytokines, Am J Respir Cell Mol Biol, 14, 45, 10.1165/ajrcmb.14.1.8534485 Weber, 1996, Differential regulation of b1 and b2 integrin avidity by chemoattractants in eosinophils, Proc Natl Acad Sci USA, 93, 10939, 10.1073/pnas.93.20.10939 Tachimoto, 2000, CCR3-active chemokines promote rapid detachment of eosinophils from VCAM-1 in vitro, J Immunol, 165, 2748, 10.4049/jimmunol.165.5.2748 Minshall, 1998, Interleukin-5 expression in the bone marrow of sensitized Balb/c mice after allergen challenge, Am J Respir Crit Care Med, 158, 951, 10.1164/ajrccm.158.3.9709114 Groopman, 1987, Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome, N Engl J Med, 317, 593, 10.1056/NEJM198709033171003 Shi, 1998, Effect of inhaled interleukin-5 on airway hyperreactivity and eosinophilia in asthmatics, Am J Respir Crit Care Med, 157, 204, 10.1164/ajrccm.157.1.9703027 Bochner, 1991, Episodic eosinophilia-myalgia-like syndrome in a patient without L-tryptophan use: association with eosinophil activation and increased serum levels of granulocyte-macrophage colony-stimulating factor, J Allergy Clin Immunol, 88, 629, 10.1016/0091-6749(91)90157-J Butterfield, 1992, Elevated serum levels of interleukin-5 in patients with the syndrome of episodic angioedema and eosinophilia, Blood, 79, 688, 10.1182/blood.V79.3.688.688 Fang, 1994, Increased circulating levels of interleukin-5 in a case of steroid-resistant hypereosinophilic syndrome with ileal involvement, J Allergy Clin Immunol, 94, 129, 10.1016/0091-6749(94)90079-5 Simon, 1999, Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia, N Engl J Med, 341, 1112, 10.1056/NEJM199910073411503 Mishra, 1999, Fundamental signals that regulate eosinophil homing to the gastrointestinal tract, J Clin Invest, 103, 1719, 10.1172/JCI6560 Winkel, 1981, Within-day physiologic variation of leukocyte types in healthy subjects as assayed by two automated leukocyte differential analyzers, Am J Clin Pathol, 75, 693, 10.1093/ajcp/75.5.693 Bochner, 2004, Adhesion molecules as therapeutic targets, Immunol Allergy Clin North Am, 24, 615, 10.1016/j.iac.2004.06.003 Gauvreau, 2003, The effects of an anti-CD11a mAb, efalizumab, on allergen-induced airway responses and airway inflammation in subjects with atopic asthma, J Allergy Clin Immunol, 112, 331, 10.1067/mai.2003.1689 Shi, 2000, Lymph node trafficking and antigen presentation by endobronchial eosinophils, J Clin Invest, 105, 945, 10.1172/JCI8945 Conus, 2005, Leptin is an eosinophil survival factor, J Allergy Clin Immunol, 116, 1228, 10.1016/j.jaci.2005.09.003 Bureau, 2002, CD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: possible involvement in allergic inflammation, J Allergy Clin Immunol, 110, 443, 10.1067/mai.2002.126781 Rothenberg, 2006, The eosinophil, Annu Rev Immunol, 24, 147, 10.1146/annurev.immunol.24.021605.090720 Simon, 1997, Direct demonstration of delayed eosinophil apoptosis as a mechanism causing tissue eosinophilia, J Immunol, 158, 3902, 10.4049/jimmunol.158.8.3902 Cameron, 2000, Evidence for local eosinophil differentiation within allergic nasal mucosa: inhibition with soluble IL-5 receptor, J Immunol, 164, 1538, 10.4049/jimmunol.164.3.1538 Denburg, 2004, Systemic aspects of chronic rhinosinusitis, Immunol Allergy Clin North Am, 24, 87, 10.1016/S0889-8561(03)00106-1 Broide, 1992, Cytokines in symptomatic asthma airways, J Allergy Clin Immunol, 89, 958, 10.1016/0091-6749(92)90218-Q Kroegel, 1994, Blood and bronchoalveolar eosinophils in allergic subjects following segmental antigen challenge: surface phenotype, density heterogeneity, and prostanoid production, J Allergy Clin Immunol, 93, 725, 10.1016/0091-6749(94)90252-6 Esnault, 2002, GM-CSF regulation in eosinophils, Arch Immunol Ther Exp (Warsz), 50, 121 Rosenberg, 2007, Eosinophil trafficking in allergy and asthma, J Allergy Clin Immunol, 119, 1303, 10.1016/j.jaci.2007.03.048 Fryer, 1997, Antibody to VLA-4, but not to L-selectin, protects neuronal M2 muscarinic receptors in antigen-challenged guinea pig airways, J Clin Invest, 99, 2036, 10.1172/JCI119372 Gonzalo, 1996, Eosinophil recruitment to the lung in a murine model of allergic inflammation—the role of T cells, chemokines, and adhesion receptors, J Clin Invest, 98, 2332, 10.1172/JCI119045 Gonzalo, 1998, The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness, J Exp Med, 188, 157, 10.1084/jem.188.1.157 Norris, 2005, Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma, J Allergy Clin Immunol, 116, 761, 10.1016/j.jaci.2005.04.045 Pero, 2007, Galphai2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation, Proc Natl Acad Sci U S A, 104, 4371, 10.1073/pnas.0700185104 Anwar, 1993, Adhesion to fibronectin prolongs eosinophil survival, J Exp Med, 177, 839, 10.1084/jem.177.3.839 Georas, 1993, Expression of a functional laminin receptor (a6b1, VLA-6) on human eosinophils, Blood, 82, 2872, 10.1182/blood.V82.9.2872.2872 Bochner, 2003, Cellular adhesion in inflammation, 117 Broide, 1998, Inhibition of pulmonary eosinophilia in P-selectin- and ICAM-1-deficient mice, Am J Respir Cell Mol Biol, 18, 218, 10.1165/ajrcmb.18.2.2829 Bochner, 2000, Road signs guiding leukocytes along the inflammation superhighway, J Allergy Clin Immunol, 106, 817, 10.1067/mai.2000.110813 Broide, 2001, Eosinophil trafficking to sites of allergic inflammation, Immunol Rev, 179, 163, 10.1034/j.1600-065X.2001.790116.x Wardlaw, 1999, Molecular basis for selective eosinophil trafficking in asthma: a multistep paradigm, J Allergy Clin Immunol, 104, 917, 10.1016/S0091-6749(99)70069-2 Bochner, 1994, Differences between human eosinophils and neutrophils in the function and expression of sialic acid-containing counterligands for E-selectin, J Immunol, 152, 774, 10.4049/jimmunol.152.2.774 Broide, 2002, Core 2 oligosaccharides mediate eosinophil and neutrophil peritoneal but not lung recruitment, Am J Physiol Lung Cell Mol Physiol, 282, L259, 10.1152/ajplung.00214.2001 Beeh, 2006, Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial, Pulm Pharmacol Ther, 19, 233, 10.1016/j.pupt.2005.07.004 Meyer, 2007, Tolerability and pharmacokinetics of inhaled bimosiamose disodium in healthy males, Br J Clin Pharmacol, 63, 451, 10.1111/j.1365-2125.2006.02775.x Kita, 2003, Biology of eosinophils, 305 Prin, 1983, Heterogeneity of human peripheral blood eosinophils: variability in cell density and cytotoxic ability in relation to the level and the origin of hypereosinophilia, Int Arch Allergy Appl Immunol, 72, 336, 10.1159/000234893 Fukuda, 1985, Increased numbers of hypodense eosinophils in the blood of patients with bronchial asthma, Am Rev Respir Dis, 132, 981 Caulfield, 1990, A morphometric study of normodense and hypodense human eosinophils that are derived in vivo and in vitro, Am J Pathol, 137, 27 Matsumoto, 1998, CD44 and CD69 represent different types of cell surface activation markers for human eosinophils, Am J Respir Cell Mol Biol, 18, 860, 10.1165/ajrcmb.18.6.3159 Koenderman, 1996, Eosinophil priming by cytokines: from cellular signal to in vivo modulation, Eur Respir J Suppl, 22, 119s Brandt, 2006, The alpha4bbeta7-integrin is dynamically expressed on murine eosinophils and involved in eosinophil trafficking to the intestine, Clin Exp Allergy, 36, 543, 10.1111/j.1365-2222.2006.02456.x Blanchard, 2006, Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis, J Clin Invest, 116, 536, 10.1172/JCI26679 Katoh, 2003, A role for CD44 in an antigen-induced murine model of pulmonary eosinophilia, J Clin Invest, 111, 1563, 10.1172/JCI16583 Zimmermann, 2003, Chemokines in asthma: cooperative interaction between chemokines and IL-13, J Allergy Clin Immunol, 111, 227, 10.1067/mai.2003.139 Menzies-Gow, 2002, Eotaxin (CCL11) and eotaxin-2 (CCL24) induce recruitment of eosinophils, basophils, neutrophils, and macrophages as well as features of early- and late-phase allergic reactions following cutaneous injection in human atopic and nonatopic volunteers, J Immunol, 169, 2712, 10.4049/jimmunol.169.5.2712 Beck, 1997, Cutaneous injection of RANTES causes eosinophil recruitment: comparison of nonallergic and allergic human subjects, J Immunol, 159, 2962, 10.4049/jimmunol.159.6.2962 Pereira, 2003, Effects of anti-eotaxin monoclonal antibody CAT-213 on allergen-induced rhinitis, J Allergy Clin Immunol, 111, S268, 10.1016/S0091-6749(03)80960-0 Main, 2006, A potent human anti-eotaxin1 antibody, CAT-213: isolation by phage display and in vitro and in vivo efficacy, J Pharmacol Exp Ther, 319, 1395, 10.1124/jpet.106.110734 Moqbel, 1999, Exocytotic events in eosinophils and mast cells, Clin Exp Allergy, 29, 1017, 10.1046/j.1365-2222.1999.00633.x Tager, 2000, 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, 192, 439, 10.1084/jem.192.3.439 Nagata, 1999, CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s), FEBS Lett, 459, 195, 10.1016/S0014-5793(99)01251-X Hirai, 2001, Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2, J Exp Med, 193, 255, 10.1084/jem.193.2.255 O'Reilly, 2002, Identification of a histamine H4 receptor on human eosinophils–role in eosinophil chemotaxis, J Recept Signal Transduct Res, 22, 431, 10.1081/RRS-120014612 Sihra, 1997, Expression of high-affinity IgE receptors (FceRI) on peripheral blood basophils, monocytes, and eosinophils in atopic and nonatopic subjects: relationship to total serum IgE concentrations, J Allergy Clin Immunol, 99, 699, 10.1016/S0091-6749(97)70033-2 Kita, 1999, Does IgE bind to and activate eosinophils from patients with allergy?, J Immunol, 162, 6901, 10.4049/jimmunol.162.11.6901 Kayaba, 2001, Human eosinophils and human high affinity IgE receptor transgenic mouse eosinophils express low levels of high affinity IgE receptor, but release IL-10 upon receptor activation, J Immunol, 167, 995, 10.4049/jimmunol.167.2.995 Bandeira-Melo, 2003, Eosinophils and cysteinyl leukotrienes, Prostaglandins Leukot Essent Fatty Acids, 69, 135, 10.1016/S0952-3278(03)00074-7 Gharaee-Kermani, 1998, The role of eosinophils in pulmonary fibrosis, Int J Mol Med, 1, 43 Levi-Schaffer, 1999, Human eosinophils regulate human lung- and skin-derived fibroblast properties in vitro: a role for transforming growth factor beta (TGF-beta), Proc Natl Acad Sci U S A, 96, 9660, 10.1073/pnas.96.17.9660 Spry, 1989, The pathogenesis of endomyocardial fibrosis: the role of the eosinophil, Springer Semin Immunopathol, 11, 471, 10.1007/BF00201883 Dvorak, 1992, Mature eosinophils stimulated to develop in human-cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. II. Vesicular transport of specific granule matrix peroxidase, a mechanism for effecting piecemeal degranulation, Am J Pathol, 140, 795 Melo, 2005, Intragranular vesiculotubular compartments are involved in piecemeal degranulation by activated human eosinophils, Traffic, 6, 866, 10.1111/j.1600-0854.2005.00322.x Logan, 2003, Understanding exocytosis in immune and inflammatory cells: the molecular basis of mediator secretion, J Allergy Clin Immunol, 111, 923, 10.1016/S0091-6749(03)80114-8 Moqbel, 2006, Differential secretion of cytokines, Sci STKE, 338, 26 Dvorak, 1990, Subcellular morphology and biochemistry of eosinophils, vol. 2, 237 Gleich, 2000, Mechanisms of eosinophil-associated inflammation, J Allergy Clin Immunol, 105, 651, 10.1067/mai.2000.105712 Martin, 1996, Eosinophils in allergy: role in disease, degranulation, and cytokines, Int Arch Allergy Immunol, 109, 207, 10.1159/000237239 Thomas, 2000, Inflammatory cell activation by eosinophil granule proteins, Chem Immunol, 76, 99, 10.1159/000058783 Jacoby, 2001, Eosinophil recruitment to the airway nerves, J Allergy Clin Immunol, 107, 211, 10.1067/mai.2001.112940 Rochester, 1996, Eosinophil-fibroblast 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, 156, 4449, 10.4049/jimmunol.156.11.4449 Sedgwick, 1992, Comparison of airway and blood eosinophil function after in vivo antigen challenge, J Immunol, 149, 3710, 10.4049/jimmunol.149.11.3710 Gleich, 1996, Glucocorticoid effects on human eosinophils, 279 Stellato, 1999, Differential regulation of epithelial-derived C-C chemokine expression by IL-4 and the glucocorticoid budesonide, J Immunol, 163, 5624, 10.4049/jimmunol.163.10.5624 Druilhe, 2003, Glucocorticoid-induced apoptosis in human eosinophils: mechanisms of action, Apoptosis, 8, 481, 10.1023/A:1025590308147 Fan, 2005, The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy, Eur Respir J, 26, 933, 10.1183/09031936.05.00120204 Simon, 2006, Molecules involved in the regulation of eosinophil apoptosis, Chem Immunol Allergy, 91, 49, 10.1159/000090229 Okada, 1998, Lidocaine and its analogues inhibit IL-5-mediated survival and activation of human eosinophils, J Immunol, 160, 4010, 10.4049/jimmunol.160.8.4010 Alam, 1994, Transforming growth factor beta abrogates the effects of hematopoietins on eosinophils and induces their apoptosis, J Exp Med, 179, 1041, 10.1084/jem.179.3.1041 Nutku, 2003, Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis, Blood, 101, 5014, 10.1182/blood-2002-10-3058 Zhang, 2007, Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils, Blood, 109, 4280, 10.1182/blood-2006-08-039255 Matsumoto, 1995, Induction of apoptosis in human eosinophils by anti-fas antibody treatment in vitro, Blood, 86, 1437, 10.1182/blood.V86.4.1437.bloodjournal8641437 Matsumoto, 2004, Extremely rapid and intense induction of apoptosis in human eosinophils by anti-CD30 antibody treatment in vitro, J Immunol, 172, 2186, 10.4049/jimmunol.172.4.2186 von Gunten, 2007, Intravenous immunoglobulin preparations contain anti-Siglec-8 autoantibodies, J Allergy Clin Immunol, 119, 1005, 10.1016/j.jaci.2007.01.023 Klion, 2006, Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report, J Allergy Clin Immunol, 117, 1292, 10.1016/j.jaci.2006.02.042 Cools, 2003, A tyrosine kinase created by fusion of the PDGFRα and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome, N Engl J Med, 348, 1201, 10.1056/NEJMoa025217 Munitz, 2006, Reversal of airway inflammation and remodeling in asthma by a bispecific antibody fragment linking CCR3 to CD300a, J Allergy Clin Immunol, 118, 1082, 10.1016/j.jaci.2006.07.041 Ackerman, 2004, Eosinophilia, eosinophil-associated diseases and the hypereosinophilic syndromes, 763 Klion, 2006, Safety and tolerability of anti-IL-5 monoclonal antibody (Mepolizumab) therapy in patients with HES: a multicenter, randomized, double-blind, placebo-controlled trial, Blood [ASH Annual Meeting Abstracts], 108, 2694 Yamada, 2006, The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease, Blood, 107, 4071, 10.1182/blood-2005-08-3153