Expression of interleukin-5- and granulocyte macrophage-colony-stimulating factor-responsive genes in blood and airway eosinophils.

Because interleukin (IL)-5 family cytokines are critical regulators of eosinophil development, recruitment, and activation, this study was initiated to identify proteins induced by these cytokines in eosinophils. Using oligonucleotide microarrays, numerous transcripts were identified as responsive to both IL-5 and granulocyte macrophage-colony-stimulating factor (GM-CSF), but no transcripts were markedly affected by one cytokine and not the other. Expression of several gene products were seen to be increased following in vitro stimulation of human blood eosinophils, including the IL-3 receptor alpha subunit, lymphotoxin beta, Pim-1, and cyclin D3. Given that eosinophils recovered from the bronchoalveolar lavage fluid of allergic patients after antigen challenge are exposed to IL-5 or GM-CSF in the airway prior to isolation, the hypothesis was tested that selected IL-5- and GM-CSF-responsive genes are upregulated in airway eosinophils relative to the expression in blood cells. Airway eosinophils displayed greater cell surface expression of the IL-3 receptor alpha subunit, CD44, CD25, and CD66e, suggesting that these proteins may be markers of eosinophil activation by IL-5 family cytokines in airway eosinophils. Other genes that were induced by both IL-5 and GM-CSF showed protein expression at similar or decreased levels in airway eosinophils relative to their circulating counterparts (i.e., lymphotoxin beta and CD24). These studies have identified several transcriptional targets of IL-5 and GM-CSF in human eosinophils and suggest that a number of protein products are critical to the responsiveness of airway eosinophils.

[1]  Lin Ying Liu,et al.  IL-5 and Granulocyte-Macrophage Colony-Stimulating Factor Activate STAT3 and STAT5 and Promote Pim-1 and Cyclin D3 Protein Expression in Human Eosinophils1 , 2004, The Journal of Immunology.

[2]  Lin Ying Liu,et al.  Decreased Expression of Membrane IL-5 Receptor α on Human Eosinophils: I. Loss of Membrane IL-5 Receptor α on Airway Eosinophils and Increased Soluble IL-5 Receptor α in the Airway After Allergen Challenge1 , 2002, The Journal of Immunology.

[3]  Mei X. Wu,et al.  Impaired apoptosis, extended duration of immune responses, and a lupus-like autoimmune disease in IEX-1-transgenic mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  S. Esnault,et al.  Y Box-Binding Factor Promotes Eosinophil Survival by Stabilizing Granulocyte-Macrophage Colony-Stimulating Factor mRNA1 , 2001, The Journal of Immunology.

[5]  S. Phipps,et al.  Microarray analysis of eosinophils reveals a number of candidate survival and apoptosis genes. , 2001, American journal of respiratory cell and molecular biology.

[6]  K. Ohta,et al.  Chemokine receptor expression profile of eosinophils at inflamed tissue sites: Decreased CCR3 and increased CXCR4 expression by lung eosinophils. , 2001, The Journal of allergy and clinical immunology.

[7]  A. McKenzie,et al.  Elemental signals regulating eosinophil accumulation in the lung , 2001, Immunological reviews.

[8]  C. Li,et al.  Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  W. Busse,et al.  Inhaled budesonide decreases airway inflammatory response to allergen. , 2000, American journal of respiratory and critical care medicine.

[10]  M. Bates,et al.  ERK1 and ERK2 Activation by Chemotactic Factors in Human Eosinophils Is Interleukin 5-dependent and Contributes to Leukotriene C4 Biosynthesis* , 2000, The Journal of Biological Chemistry.

[11]  S. Esnault,et al.  Primary peripheral blood eosinophils rapidly degrade transfected granulocyte-macrophage colony-stimulating factor mRNA. , 1999, Journal of immunology.

[12]  S. Holgate,et al.  Cytokine profiles of BAL T cells and T‐cell clones obtained from human asthmatic airways after local allergen challenge , 1999, Allergy.

[13]  M. Culbertson,et al.  Yeast Upf Proteins Required for RNA Surveillance Affect Global Expression of the Yeast Transcriptome , 1999, Molecular and Cellular Biology.

[14]  E. Gelfand,et al.  Role of IL–5 in the Development of Allergen–Induced Airway Hyperresponsiveness , 1999, International Archives of Allergy and Immunology.

[15]  W. Luttmann,et al.  CD69 surface expression on human lung eosinophils after segmental allergen provocation. , 1999, The European respiratory journal.

[16]  M. Lindsay,et al.  Pharmacology of the eosinophil. , 1999, Pharmacological reviews.

[17]  S. Hammarström.  The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. , 1999, Seminars in cancer biology.

[18]  M. Isobe,et al.  Eosinophil active cytokines and surface analysis of eosinophils in Churg-Strauss syndrome. , 1999, Allergy and asthma proceedings.

[19]  S. Uh,et al.  Granulocyte macrophage colony-stimulating factor is the main cytokine enhancing survival of eosinophils in asthmatic airways. , 1998, The European respiratory journal.

[20]  W. Busse,et al.  Interleukin 5 signals through Shc and Grb2 in human eosinophils. , 1998, American journal of respiratory cell and molecular biology.

[21]  K. Matsumoto,et al.  CD44 and CD69 represent different types of cell-surface activation markers for human eosinophils. , 1998, American journal of respiratory cell and molecular biology.

[22]  C. Benjamin,et al.  Antibodies to lymphotoxin α (LTα) and LTβ recognize different glial cell types in the central nervous system , 1997, Journal of Neuroimmunology.

[23]  W. Busse,et al.  The immediate and late allergic response to segmental bronchopulmonary provocation in asthma. , 1997, American journal of respiratory and critical care medicine.

[24]  P. Altevogt,et al.  CD24, a mucin-type glycoprotein, is a ligand for P-selectin on human tumor cells. , 1997, Blood.

[25]  H. Simon,et al.  Activation of signaling pathways and prevention of apoptosis by cytokines in eosinophils. , 1997, International archives of allergy and immunology.

[26]  P. Coffer,et al.  Eosinophil priming by cytokines: from cellular signal to in vivo modulation. , 1996, The European respiratory journal. Supplement.

[27]  A. Skubitz,et al.  CD66a, CD66b, CD66c, and CD66d each Independently stimulate neutrophils , 1996, Journal of leukocyte biology.

[28]  D. Stephany,et al.  Identification of surface molecules associated with physiologic activation of eosinophils. Application of whole-blood flow cytometry to eosinophils. , 1996, Journal of immunology.

[29]  M. van de Rijn,et al.  Eotaxin Triggers Eosmophil-Selective Chemotaxis and Calcium Flux via a Distinct Receptor and Induces Pulmonary Eosinophilia in the Presence of Interleukin 5 in Mice , 1996, Molecular medicine.

[30]  M. Jordana,et al.  Interleukin-3 in bronchial biopsies from nonasthmatics and patients with mild and allergen-induced asthma. , 1996, American journal of respiratory and critical care medicine.

[31]  M. Wadhwa,et al.  Evidence for a signaling role for the alpha chains of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors: divergent signaling pathways between GM-CSF/IL-3 and IL-5. , 1995, Blood.

[32]  J. Tavernier,et al.  Characterization of critical residues in the cytoplasmic domain of the human interleukin‐5 receptor α chain required for growth signal transduction , 1995, European journal of immunology.

[33]  C. Ware,et al.  The ligands and receptors of the lymphotoxin system. , 1995, Current topics in microbiology and immunology.

[34]  T. Walz,et al.  Transforming growth factor alpha expression in normal human blood eosinophils: differential regulation by granulocyte-macrophage colony-stimulating factor and interleukin-3. , 1994, Leukemia.

[35]  R. Rees,et al.  Changes in the phenotypic characteristics of eosinophils from patients receiving recombinant human interleukin‐2 (rhIL‐2) therapy , 1994, British journal of haematology.

[36]  L. Lichtenstein,et al.  Blood and bronchoalveolar eosinophils in allergic subjects after segmental antigen challenge: surface phenotype, density heterogeneity, and prostanoid production. , 1994, The Journal of allergy and clinical immunology.

[37]  W. Busse,et al.  Comparison of airway and blood eosinophil function after in vivo antigen challenge. , 1992, Journal of immunology.

[38]  K. Blaser,et al.  An improved immunomagnetic procedure for the isolation of highly purified human blood eosinophils. , 1991, Journal of immunological methods.

[39]  W. Busse,et al.  Immediate and late airway response of allergic rhinitis patients to segmental antigen challenge. Characterization of eosinophil and mast cell mediators. , 1991, The American review of respiratory disease.

[40]  J. Gamble,et al.  Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival. , 1986, The Journal of clinical investigation.