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. 1997 Oct 1;100(7):1657–1666. doi: 10.1172/JCI119690

Chemokine-induced eosinophil recruitment. Evidence of a role for endogenous eotaxin in an in vivo allergy model in mouse skin.

M M Teixeira 1, T N Wells 1, N W Lukacs 1, A E Proudfoot 1, S L Kunkel 1, T J Williams 1, P G Hellewell 1
PMCID: PMC508348  PMID: 9312163

Abstract

Selective eosinophil recruitment into tissues is a characteristic feature of allergic diseases. Chemokines are effective leukocyte chemoattractants and may play an important role in mediating eosinophil recruitment in various allergic conditions in man. Here, we describe a novel mouse model of eosinophil recruitment in which we have compared the in vivo chemoattractant activity of different C-C chemokines. Furthermore, we describe the use of antibodies to chemokines and receptor blockade to address the endogenous mechanisms involved in eosinophil recruitment in a late-phase allergic reaction in mouse skin. Intradermal injection of mEotaxin and mMIP-1alpha, but not mMCP-1, mRANTES, mMCP-5, or mMIP-1beta, induced significant 111In-eosinophil recruitment in mouse skin. Significant 111In-eosinophil recruitment was also observed in an active cutaneous anaphylactic reaction. Pretreatment of skin sites with antieotaxin antiserum, but not an antiMIP-1alpha antibody, suppressed 111In-eosinophil recruitment in this delayed-onset allergic reaction. Similarly, desensitization of the eosinophil eotaxin receptor CCR3 with mEotaxin, or blockade of the receptor with metRANTES, significantly inhibited 111In-eosinophil recruitment in the allergic reaction. These results demonstrate an important role for endogenous eotaxin in mediating the 111In-eosinophil recruitment in allergic inflammation, and suggest that blockade of the CCR3 receptor is a valid strategy to inhibit eosinophil migration in vivo.

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Selected References

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  1. Alam R., Kumar D., Anderson-Walters D., Forsythe P. A. Macrophage inflammatory protein-1 alpha and monocyte chemoattractant peptide-1 elicit immediate and late cutaneous reactions and activate murine mast cells in vivo. J Immunol. 1994 Feb 1;152(3):1298–1303. [PubMed] [Google Scholar]
  2. Bacon K. B., Schall T. J. Chemokines as mediators of allergic inflammation. Int Arch Allergy Immunol. 1996 Feb;109(2):97–109. doi: 10.1159/000237207. [DOI] [PubMed] [Google Scholar]
  3. Bazan J. F., Bacon K. B., Hardiman G., Wang W., Soo K., Rossi D., Greaves D. R., Zlotnik A., Schall T. J. A new class of membrane-bound chemokine with a CX3C motif. Nature. 1997 Feb 13;385(6617):640–644. doi: 10.1038/385640a0. [DOI] [PubMed] [Google Scholar]
  4. Das A. M., Flower R. J., Hellewell P. G., Teixeira M. M., Perretti M. A novel murine model of allergic inflammation to study the effect of dexamethasone on eosinophil recruitment. Br J Pharmacol. 1997 May;121(1):97–104. doi: 10.1038/sj.bjp.0701122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Daugherty B. L., Siciliano S. J., DeMartino J. A., Malkowitz L., Sirotina A., Springer M. S. Cloning, expression, and characterization of the human eosinophil eotaxin receptor. J Exp Med. 1996 May 1;183(5):2349–2354. doi: 10.1084/jem.183.5.2349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dent L. A., Strath M., Mellor A. L., Sanderson C. J. Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med. 1990 Nov 1;172(5):1425–1431. doi: 10.1084/jem.172.5.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Djukanović R., Roche W. R., Wilson J. W., Beasley C. R., Twentyman O. P., Howarth R. H., Holgate S. T. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. doi: 10.1164/ajrccm/142.2.434. [DOI] [PubMed] [Google Scholar]
  8. Faccioli L. H., Nourshargh S., Moqbel R., Williams F. M., Sehmi R., Kay A. B., Williams T. J. The accumulation of 111In-eosinophils induced by inflammatory mediators, in vivo. Immunology. 1991 Jun;73(2):222–227. [PMC free article] [PubMed] [Google Scholar]
  9. Ganzalo J. A., Jia G. Q., Aguirre V., Friend D., Coyle A. J., Jenkins N. A., Lin G. S., Katz H., Lichtman A., Copeland N. Mouse Eotaxin expression parallels eosinophil accumulation during lung allergic inflammation but it is not restricted to a Th2-type response. Immunity. 1996 Jan;4(1):1–14. doi: 10.1016/s1074-7613(00)80293-9. [DOI] [PubMed] [Google Scholar]
  10. Gao J. L., Murphy P. M. Cloning and differential tissue-specific expression of three mouse beta chemokine receptor-like genes, including the gene for a functional macrophage inflammatory protein-1 alpha receptor. J Biol Chem. 1995 Jul 21;270(29):17494–17501. doi: 10.1074/jbc.270.29.17494. [DOI] [PubMed] [Google Scholar]
  11. Gao J. L., Sen A. I., Kitaura M., Yoshie O., Rothenberg M. E., Murphy P. M., Luster A. D. Identification of a mouse eosinophil receptor for the CC chemokine eotaxin. Biochem Biophys Res Commun. 1996 Jun 25;223(3):679–684. doi: 10.1006/bbrc.1996.0955. [DOI] [PubMed] [Google Scholar]
  12. Gonzalo J. A., Lloyd C. M., Kremer L., Finger E., Martinez-A C., Siegelman M. H., Cybulsky M., Gutierrez-Ramos J. C. 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 Nov 15;98(10):2332–2345. doi: 10.1172/JCI119045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  14. Heath H., Qin S., Rao P., Wu L., LaRosa G., Kassam N., Ponath P. D., Mackay C. R. Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody. J Clin Invest. 1997 Jan 15;99(2):178–184. doi: 10.1172/JCI119145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jia G. Q., Gonzalo J. A., Lloyd C., Kremer L., Lu L., Martinez-A C., Wershil B. K., Gutierrez-Ramos J. C. Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation. J Exp Med. 1996 Nov 1;184(5):1939–1951. doi: 10.1084/jem.184.5.1939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jose P. J., Griffiths-Johnson D. A., Collins P. D., Walsh D. T., Moqbel R., Totty N. F., Truong O., Hsuan J. J., Williams T. J. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med. 1994 Mar 1;179(3):881–887. doi: 10.1084/jem.179.3.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kameyoshi Y., Dörschner A., Mallet A. I., Christophers E., Schröder J. M. Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992 Aug 1;176(2):587–592. doi: 10.1084/jem.176.2.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Karpus W. J., Lukacs N. W., McRae B. L., Strieter R. M., Kunkel S. L., Miller S. D. An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis. J Immunol. 1995 Nov 15;155(10):5003–5010. [PubMed] [Google Scholar]
  19. Kita H., Gleich G. J. Chemokines active on eosinophils: potential roles in allergic inflammation. J Exp Med. 1996 Jun 1;183(6):2421–2426. doi: 10.1084/jem.183.6.2421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Leiferman K. M. Eosinophils in atopic dermatitis. Allergy. 1989;44 (Suppl 9):20–26. [PubMed] [Google Scholar]
  21. Lukacs N. W., Kunkel S. L., Strieter R. M., Warmington K., Chensue S. W. The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation. J Exp Med. 1993 Jun 1;177(6):1551–1559. doi: 10.1084/jem.177.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lukacs N. W., Strieter R. M., Chensue S. W., Kunkel S. L. Activation and regulation of chemokines in allergic airway inflammation. J Leukoc Biol. 1996 Jan;59(1):13–17. doi: 10.1002/jlb.59.1.13. [DOI] [PubMed] [Google Scholar]
  23. Lukacs N. W., Strieter R. M., Shaklee C. L., Chensue S. W., Kunkel S. L. Macrophage inflammatory protein-1 alpha influences eosinophil recruitment in antigen-specific airway inflammation. Eur J Immunol. 1995 Jan;25(1):245–251. doi: 10.1002/eji.1830250140. [DOI] [PubMed] [Google Scholar]
  24. Mackay C. R. Chemokine receptors and T cell chemotaxis. J Exp Med. 1996 Sep 1;184(3):799–802. doi: 10.1084/jem.184.3.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Marleau S., Griffiths-Johnson D. A., Collins P. D., Bakhle Y. S., Williams T. J., Jose P. J. Human RANTES acts as a receptor antagonist for guinea pig eotaxin in vitro and in vivo. J Immunol. 1996 Nov 1;157(9):4141–4146. [PubMed] [Google Scholar]
  26. Meurer R., Van Riper G., Feeney W., Cunningham P., Hora D., Jr, Springer M. S., MacIntyre D. E., Rosen H. Formation of eosinophilic and monocytic intradermal inflammatory sites in the dog by injection of human RANTES but not human monocyte chemoattractant protein 1, human macrophage inflammatory protein 1 alpha, or human interleukin 8. J Exp Med. 1993 Dec 1;178(6):1913–1921. doi: 10.1084/jem.178.6.1913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Murphy P. M. Chemokine receptors: structure, function and role in microbial pathogenesis. Cytokine Growth Factor Rev. 1996 Jun;7(1):47–64. doi: 10.1016/1359-6101(96)00009-3. [DOI] [PubMed] [Google Scholar]
  28. Ponath P. D., Qin S., Post T. W., Wang J., Wu L., Gerard N. P., Newman W., Gerard C., Mackay C. R. Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med. 1996 Jun 1;183(6):2437–2448. doi: 10.1084/jem.183.6.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ponath P. D., Qin S., Ringler D. J., Clark-Lewis I., Wang J., Kassam N., Smith H., Shi X., Gonzalo J. A., Newman W. Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils. J Clin Invest. 1996 Feb 1;97(3):604–612. doi: 10.1172/JCI118456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Post T. W., Bozic C. R., Rothenberg M. E., Luster A. D., Gerard N., Gerard C. Molecular characterization of two murine eosinophil beta chemokine receptors. J Immunol. 1995 Dec 1;155(11):5299–5305. [PubMed] [Google Scholar]
  31. Power C. A., Wells T. N. Cloning and characterization of human chemokine receptors. Trends Pharmacol Sci. 1996 Jun;17(6):209–213. doi: 10.1016/0165-6147(96)10019-5. [DOI] [PubMed] [Google Scholar]
  32. Proudfoot A. E., Power C. A., Hoogewerf A. J., Montjovent M. O., Borlat F., Offord R. E., Wells T. N. Extension of recombinant human RANTES by the retention of the initiating methionine produces a potent antagonist. J Biol Chem. 1996 Feb 2;271(5):2599–2603. doi: 10.1074/jbc.271.5.2599. [DOI] [PubMed] [Google Scholar]
  33. Rot A., Krieger M., Brunner T., Bischoff S. C., Schall T. J., Dahinden C. A. RANTES and macrophage inflammatory protein 1 alpha induce the migration and activation of normal human eosinophil granulocytes. J Exp Med. 1992 Dec 1;176(6):1489–1495. doi: 10.1084/jem.176.6.1489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rothenberg M. E., Ownbey R., Mehlhop P. D., Loiselle P. M., van de Rijn M., Bonventre J. V., Oettgen H. C., Leder P., Luster A. D. Eotaxin triggers eosinophil-selective chemotaxis and calcium flux via a distinct receptor and induces pulmonary eosinophilia in the presence of interleukin 5 in mice. Mol Med. 1996 May;2(3):334–348. [PMC free article] [PubMed] [Google Scholar]
  35. Sabroe I., Williams T. J., Hébert C. A., Collins P. D. Chemoattractant cross-desensitization of the human neutrophil IL-8 receptor involves receptor internalization and differential receptor subtype regulation. J Immunol. 1997 Feb 1;158(3):1361–1369. [PubMed] [Google Scholar]
  36. Sarafi M. N., Garcia-Zepeda E. A., MacLean J. A., Charo I. F., Luster A. D. Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a structural and functional homologue of human MCP-1. J Exp Med. 1997 Jan 6;185(1):99–109. doi: 10.1084/jem.185.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schall T. J., Bacon K. B. Chemokines, leukocyte trafficking, and inflammation. Curr Opin Immunol. 1994 Dec;6(6):865–873. doi: 10.1016/0952-7915(94)90006-x. [DOI] [PubMed] [Google Scholar]
  38. Teixeira M. M., Giembycz M. A., Lindsay M. A., Hellewell P. G. Pertussis toxin shows distinct early signalling events in platelet-activating factor-, leukotriene B4-, and C5a-induced eosinophil homotypic aggregation in vitro and recruitment in vivo. Blood. 1997 Jun 15;89(12):4566–4573. [PubMed] [Google Scholar]
  39. Teixeira M. M., Hellewell P. G. Effect of a 5-lipoxygenase inhibitor, ZM 230487, on cutaneous allergic inflammation in the guinea-pig. Br J Pharmacol. 1994 Apr;111(4):1205–1211. doi: 10.1111/j.1476-5381.1994.tb14873.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Teixeira M. M., Rossi A. G., Williams T. J., Hellewell P. G. Effects of phosphodiesterase isoenzyme inhibitors on cutaneous inflammation in the guinea-pig. Br J Pharmacol. 1994 May;112(1):332–340. doi: 10.1111/j.1476-5381.1994.tb13073.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Teixeira M. M., Williams T. J., Hellewell P. G. Mechanisms and pharmacological manipulation of eosinophil accumulation in vivo. Trends Pharmacol Sci. 1995 Dec;16(12):418–423. doi: 10.1016/s0165-6147(00)89092-6. [DOI] [PubMed] [Google Scholar]
  42. Uguccioni M., Loetscher P., Forssmann U., Dewald B., Li H., Lima S. H., Li Y., Kreider B., Garotta G., Thelen M. Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional analogue of MCP-3 and eotaxin. J Exp Med. 1996 May 1;183(5):2379–2384. doi: 10.1084/jem.183.5.2379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Weller P. F. The immunobiology of eosinophils. N Engl J Med. 1991 Apr 18;324(16):1110–1118. doi: 10.1056/NEJM199104183241607. [DOI] [PubMed] [Google Scholar]

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