[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia

Nature Medicine volume 2, pages 449–456 (1996)Cite this article

Abstract

Eotaxin is an eosinophil–specific chemoattractant that has been recently identified in rodent models of asthma and host response against tumors. To determine whether a similar molecule might play a role in human inflammatory diseases characterized by eosinophilia, we isolated the human eotaxin gene. We demonstrate that human eotaxin is an early response gene of cytokine–stimulated epithelial and endothelial cells, and is induced in peripheral blood eosinophils by interleukin–3. Eotaxin is directly chemotactic for eosinophils, but not mononuclear cells or neutrophils. Eotaxin messenger RNA accumulates markedly in the lesions of patients with inflammatory bowel disease (ulcerative colitis and Crohn's disease), but not in the lesions of patients with diverticulitis. These results now provide a mechanism involving eotaxin to explain the eosinophil infiltration seen in a variety of human diseases; as such, an eotaxin antagonist may be a novel therapy for certain human diseases characterized by tissue eosinophilia.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gleich, G.J. & Adolphson, C.R. The eosinophilic leukocyte: Structure and function. Adv. Immunol. 39, 177–253 (1986).

    Article  CAS  Google Scholar 

  2. Weller, P.P. The immunobiology of eosinophils. N. Engl. J. Med. 324, 1110–1118 (1991).

    Article  CAS  Google Scholar 

  3. Bousquett, J. et al. Eosinophilic inflammation in asthma. N. Engl. J. Med. 323, 1033–1039 (1990).

    Article  Google Scholar 

  4. Butcher, E.G. Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity. Cell 67, 1033–1036 (1991).

    Article  CAS  Google Scholar 

  5. Baggiolini, M., Dewald, B. & Moser, B. Interleukin-8 and related chemotactic cytokines-CXC and CC chemokines. Adv. Immunol. 55, 97–179 (1994).

    Article  CAS  Google Scholar 

  6. Murphy, P.M. The molecular biology of leukocyte chemoattractant receptors. Annu. Rev. Immunol. 12, 593–633 (1994).

    Article  CAS  Google Scholar 

  7. Jose, P.J. et al. Eotaxin: A potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J. Exp. Med. 179, 881–887 (1994).

    Article  CAS  Google Scholar 

  8. Jose, P.J. et al. Eotaxin: Cloning of an eosinophils chemoattractant cytokine and increased mRNA expression in allergen-challenged guinea-pig lungs. Biochem. Biophys. Res. Commun. 205, 788–794 (1994).

    Article  CAS  Google Scholar 

  9. Rothenberg, M.E., Luster, A.D., Lilly, C.M., Drazin, J.M. & Leder, P. Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung. J. Exp. Med. 181, 1211–1216 (1994).

    Article  Google Scholar 

  10. Griffiths-Johnson, D.A., Collins, P.D., Rossi, A.G., Jose, P.J. & Williams, T.J. The chemokine, eotaxin, activates guinea-pig eosinophils in vitro and causes their accumulation into the lung in vivo. Biochem. Biophys. Res. Commun. 197, 1167–1172 (1993).

    Article  CAS  Google Scholar 

  11. Rothenberg, M.E., Luster, A.D. & Leder, P. Murine eotaxin: An eosinophil chemoattractant inducible in endothelial cells and in IL-4-induced tumor suppression. Proc. Natl Acad. Sci. USA 92, 8960–8964 (1995).

    Article  CAS  Google Scholar 

  12. Zhang, Y.J., Rutledge, J. & Rollins, B. Structure/activity analysis of human monocyte chemoattractant protein-l(MCP-l) by mutagenesis. J. Biol Chem. 269, 15918–15924 (1994).

    CAS  PubMed  Google Scholar 

  13. Gong, J.-H. & Clark-Lewis, I. Antagonists of monocyte chemoattractant protein 1 identified by modification of functionally critical NH2-terminal residues. J. Exp. Med. 181, 631–640 (1995).

    Article  CAS  Google Scholar 

  14. Shaw, G. & Kamen, R. A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46, 659–667 (1986).

    Article  CAS  Google Scholar 

  15. Jiang, Y., Valente, A.J., Williamson, M.J., Zhang, L. & Graves, D.T. Post-translational modification of a monocyte-specific chemoattractant synthesized by glioma, osteosarcoma, and vascular smooth muscle cells. J. Biol Chem. 265, 18318–18321 (1990).

    CAS  PubMed  Google Scholar 

  16. Rothenberg, M.E. et al. Eosinophils cocultured with endothelial cells have increased survival and functional properties. Science 237, 645–647 (1987).

    Article  CAS  Google Scholar 

  17. Cromwell, O. et al. Expression and generation of interleukin-8, interleukin-6 and granulocyte-macrophage colony-stimulating factor by bronchial cells and enhancement of IL-lβ and tumor necrosis factor α. Immunology 77, 330 (1992).

  18. Spry, C.J. Mechanism of eosinophilia. V. Kinetics of normal and accelerated eosinophilpoiesis. Cell Tissue Kinet. 4, 351–364 (1971).

    CAS  PubMed  Google Scholar 

  19. Mosmann, T.R. & Coffman, R.L. TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7, 145–173 (1989).

    Article  CAS  Google Scholar 

  20. Buckley, M.G. et al. IL-4 enhances IL-3 and IL-8 gene expression in a human leukemic mast cell line. Immunology 84, 410–415 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kita, H. H. et al. Granulocyte/macrophage colony-stimulating factor and inter-leukin 3 release from human peripheral blood eosinophils and neutrophils. J. Exp. Med. 174, 745–748 (1991).

    Article  CAS  Google Scholar 

  22. Rothenberg, M.E. et al. Human eosinophils have prolonged survival, enhanced functional properties, and become hypodense when exposed to human inter-leukin 3. J. Clin. Invest. 81, 1986–1992 (1988).

    Article  CAS  Google Scholar 

  23. Fuggle, W.J., Crocker, J. & Smith, P.J. A quantitative study of eosinophil poly-morphs in Hodgkin's disease. J. Clin. Pathol. 37, 267–271 (1984).

    Article  CAS  Google Scholar 

  24. Walsh, R.E. & Gaginella, T.S. The eosinophil in inflammatory bowel disease. Scand. J. Gastroenterol. 26, 1217–1224 (1991).

    Article  CAS  Google Scholar 

  25. Sarin, S.K. et al. Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis: A prospective controlled study. Dig. Dis. Sci. 32, 363–367 (1978).

    Article  Google Scholar 

  26. Willoughby, C.P., Piris, J. & Truelove, S.C. Tissue eosinophils in ulcerative colitis. Scand. J. Gastroenterol. 14, 395–399 (1979).

    CAS  PubMed  Google Scholar 

  27. Dvorak, A.M. Ultrastructural evidence for release of major basic protein-containing crystalline cores of eosinophil granules in vivo: Cytotoxic potential in Crohn's disease. J. Immunol. 125, 460–462 (1980).

    CAS  PubMed  Google Scholar 

  28. Hallgren, R. et al. Neutrophil and eosinophil involvement of the small bowel in patients with celiac disease and Crohn's disease: Studies on the secretion rate and immunohistochemical localization of granulocyte granule constituents. Am. J. Med. 86, 56–64 (1989).

    Article  CAS  Google Scholar 

  29. Dubucquoi, S. et al. Activated eosinophils and interleukin 5 expression in early recurrence of Crohn's disease. Gut 37, 242–246 (1995).

    Article  CAS  Google Scholar 

  30. Collins, P.O., Marleau, S., Griffiths-Johnson, D.A., Jose, P.J. & Williams, T.J. Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J. Exp. Med. 182, 1169–1174 (1995).

    Article  CAS  Google Scholar 

  31. Powrie, F. T cells and inflammatory bowel disease: Protective and pathogenic role. Immunity 3, 171–174 (1995).

    Article  CAS  Google Scholar 

  32. Tomonaga, M., Gasson, J.C., Quan, S.G. & Golde, D.W. Establishment of eosinophilic sublines from human promyelocytic leukemia (HL-60) cells: Demonstration of multipotentiality and single-lineage commitment of HL-60 stem cells. Blood 67, 1433–1441 (1986).

    CAS  PubMed  Google Scholar 

  33. Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. Basic local alignment search tool. J. Mol Biol. 215, 403–410 (1990).

    Article  CAS  Google Scholar 

  34. Seed, B. & Aruffo, A. Molecular cloning of the CD2 antigen, the T-cell erythro-cyte receptor, by a rapid immunoselection procedure. Proc. Natl. Acad. Sci. USA 84, 3365–3369 (1987).

    Article  CAS  Google Scholar 

  35. Hansel, T.T. et al. An improved immunomagnetic procedure for the isolation of highly purified human blood eosinophils. J. Immunol. Methods 145, 105–110 (1991).

    Article  CAS  Google Scholar 

  36. Falk, W., Goodwin, R.H. & Leonard, E.J. A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration. J. Immunol. Methods 33, 239–247 (1980).

    Article  CAS  Google Scholar 

  37. Cybulsky, M.I. et al. Alternative splicing of human VCAM-1 in activated vascular endothelium. Am. J. Pathol. 138, 815–820 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Birnstiel, M.L. & Busslinger, M. Transcription termination and 3′ processing: The end is in site! Cell 41, 349–359 (1985).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Infectious Disease Unit, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Charlestown, Massachusetts, 02129, USA

    Eduardo A. Garcia-Zepeda, Robert T. Ownbey & Andrew D. Luster

  2. Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Marc E. Rothenberg & Philip Leder

  3. Division of Immunology, Children's Hospital, Boston, Massachusetts, 02115, USA

    Jocelyn Celestin

Authors
  1. Eduardo A. Garcia-Zepeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marc E. Rothenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert T. Ownbey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jocelyn Celestin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Philip Leder
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew D. Luster
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Garcia-Zepeda, E., Rothenberg, M., Ownbey, R. et al. Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia. Nat Med 2, 449–456 (1996). https://doi.org/10.1038/nm0496-449

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0496-449

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing