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Monoclonal Antibodies to Chemokine Receptors

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Chemokine Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 138))

Abstract

Monoclonal antibodies (MAbs) to chemokine receptors are providing remarkable insight into the roles these receptors play in basal leukocyte trafficking for immune response and surveillance as well as cell specific recruitment to sites of inflammation. This latter role in particular has established chemokine receptors as attractive targets for novel antiinflammatory drug discovery. The large number of chemokines and receptors, the complex nature of their distinct and overlapping binding specificities, and the differential expression of receptors on leukocytes may provide the opportunity to develop therapeutics that selectively target subsets of leukocytes and thus avoid the broad immunosuppressive actions of most currently available antiinflammatory drugs (1). The major obstacle in the path to such therapeutics is unlikely to be the discovery and development of potent and selective chemokine receptor antagonists, inasmuch as seven transmembrane spanning G-protein couple receptors have proven to be a most successful class of drug targets (2). However, sorting through the various and complex functions mediated by a multitude chemokine receptor-ligand interactions in order to ascertain which receptor(s) is responsible for site specific recruitment of cells during initiation, progression, and maintenance of a particular disease will be a formidable task.

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References

  1. Ponath P. D. (1998) Chemokine receptor antagonists: novel therapeutics for inflammation and AIDS. Exp. Opin. Invest. Drugs 7, 1–18.

    Article  CAS  Google Scholar 

  2. Stadel J. M., Wilson S., and Bergsma D. J. (1997) Orphan G protein-coupled receptors: a neglected opportunity for pioneer drug discovery. Trends Pharm. Science 18, 430–437.

    CAS  Google Scholar 

  3. Qin S., Rottman J. B., Myers P., Kassam N., Weinblatt M., Loetscher M., et al. (1998) The chemokine receptors CXCR3 and CCR5 mark a subset of T cells associated with certain inflammatory reactions. J. Clin. Invest. 101, 746–754.

    Article  PubMed  CAS  Google Scholar 

  4. Ponath P. D., Qin S., Post T. W., Wang J., Wu L., Gerard N. P., et al. (1996) Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J. Exp. Med. 183, 2437–2448.

    Article  PubMed  CAS  Google Scholar 

  5. Heath H., Qin S., Rao P., Wu L., LaRosa G., Kassam N., et al. (1997) Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody. J. Clin. Invest. 99, 178–184.

    Article  PubMed  CAS  Google Scholar 

  6. Ying S., Robinson D. S., Meng Q., Rottman J. B., Kennedy R., Ringler D. J. (1997) Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperreactivity and predominant colocalization of eotaxin mRNA to bronchial epithelial and endothelial cells. Eur. J. Immunol. 27, 3507–3516.

    Article  PubMed  CAS  Google Scholar 

  7. Loetscher P., Seitz M., Baggiolini M., and Moser B. (1996) Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes. J. Exp. Med. 184, 569–577.

    Article  PubMed  CAS  Google Scholar 

  8. Penton-Rol G., Polentarutti N., Luini W., Borsatti A., Mancinelli R., Sica A., et al. (1998) Selective inhibition of the chemokine receptor CCR2 in human mono-cytes by INF-γ. J. Immunol. 160, 3869–3873.

    PubMed  CAS  Google Scholar 

  9. Sallusto F., Lenig D., Mackay C., and Lanzavecchia A. (1998) Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J. Exp. Med. 187, 875–883.

    Article  PubMed  CAS  Google Scholar 

  10. Foxman E. F., Campbell J. J., and Butcher E. C. (1997) Multistep navigation and the combinatorial control of leukocyte chemotaxis. J. CellBiol. 139, 1349–1360.

    Article  CAS  Google Scholar 

  11. Jones S. A., Wolf M., Qin S., Mackay C. R., and Baggiolini M. (1996) Different functions for the interleukin 8 receptors (IL-8R) of human neutrophil leukocytes: NADPH oxidase and phosolipase D are activated through IL-8R1 but not IL-8R2. Proc. Natl. Acad. Sci. USA 93, 6682–6686.

    Article  PubMed  CAS  Google Scholar 

  12. Hammond M. E. W., Lapointe G. R., Feucht P. H., Hilt S., Gallegos C. A., Gordon C. A., et al. (1995) IL-8 induces neutrophil chemotaxis predominately via type IL-8 receptors. J. Immunol. 155, 1428–1433.

    PubMed  CAS  Google Scholar 

  13. Chuntharapai A. and Kim K. J. (1995) Regulation of the expression of IL-8 receptor A/B by IL-8: possible functions of each receptor. J. Immunol. 155, 2587–2594.

    PubMed  CAS  Google Scholar 

  14. Zagorski J. and Wahl S. M. (1997) Inhibition of acute peritoneal inflammation in rats by a cytokine induced neutrophil chemoattractant receptor antagonist. J. Immunol. 159, 1059–1062.

    PubMed  CAS  Google Scholar 

  15. Gong J. H., Ratkay L. G., Waterfield J. D., and Clark-Lewis I. (1997) An antagonist of monocyte chemoattractant protein 1 (MCP-1-inhibits arthritis in the MRL-lpr mouse model. J. Exp. Med. 186, 131–137.

    Article  PubMed  CAS  Google Scholar 

  16. Lukacs N. W., Strieter R. M., Shaklee C. L., Chensue S. W., and Kunkel S. L. (1995) Macrophage inflammatory protein-1 alpha influences eosinophil recruitment in antigen-specific airway inflammation. Eur. J. Immunol. 25, 245–251.

    Article  PubMed  CAS  Google Scholar 

  17. Broaddus V. C., Boylan A. M., Hoeffel J. M., Kim K. J., Sadick M., Chuntharapai A., and Hebert C. A. (1994) Neutralization of IL-8 inhibits neutrophil influx in a rabbit model of endotoxin-induced pleurisy. J. Immunol. 152, 2960–2967.

    PubMed  CAS  Google Scholar 

  18. Rand M. L., Warren J. S., Mansour M. K., Newman W., and Ringler D. J. (1996) Inhibition of T cell recruitment and cutaneous delayed-type hypersensitivity-induced inflammation with antibodies to monocyte chemoattractant protein-1. Am. J. Path. 148, 855–864.

    PubMed  CAS  Google Scholar 

  19. VanOtteren G. M., Strieter R. M., Kunkel S. L., Paine R. R., Greenberger M. J., Danforth J. M., et al. (1995) Compartmentalized expression of RANTES in a murine model of endotoxemia. J. Immunol. 154, 1900–1908.

    PubMed  CAS  Google Scholar 

  20. Harada A., Sekido N., Akahoshi T., Wada T., Mukaida N., and Matsushima K. (1994) Essential involvement of interleukin-8 (IL-8) in acute inflammation. J. Leukoc. Biol. 5, 559–564.

    Google Scholar 

  21. Baggiolini M., Dewald B., and Moser B. (1997) Human chemokines: an update. Ann. Rev. Immunol. 15, 675–705.

    Article  CAS  Google Scholar 

  22. Weber M., Uguccioni M., Baggiolini M., Clark Lewis I., and Dahinden C. A. (1996) Deletion of the NH2-terminal residue converts monocyte chemotactic protein 1 from an activator of basophil mediator release to an eosinophil chemoattractant. J. Exp. Med. 183, 681–685.

    Article  PubMed  CAS  Google Scholar 

  23. Gong J. H., Uguccioni M., Dewald B., Baggiolini M., and Clark-Lewis I. (1996) RANTES and MCP-3 antagonists bind multiple chemokine receptors. J. Biol. Chem. 271, 10,521–10,527.

    Article  PubMed  CAS  Google Scholar 

  24. Koch A. E., Polverini P. J., Kunkel S. L., Harlow L. A., DiPietro L. A., Elner V. M., et al. (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258, 1798–1801.

    Article  PubMed  CAS  Google Scholar 

  25. Strieter R. M., Kunkel S. L., Arenberg D. A., Burdick M. D., and Polverini P. J. (1995) Interferon gamma-inducible protein 10 (IP-10), a member of the C-X-C chemokine family, is an inhibitor of angiogenesis. Biochem. Biophys. Res. Commun. 210, 51–57.

    Article  PubMed  CAS  Google Scholar 

  26. Cao Y., Chen C., Weatherbee J. A., Tsang M., and Folkman J. (1995) gro-beta, a-C-X-C-chemokine, is an angiogenesis inhibitor that suppresses the growth of Lewis lung carcinoma in mice. J. Exp. Med. 182, 2069–2077.

    Article  PubMed  CAS  Google Scholar 

  27. Graham G. J., Wright E. G., Hewick R., Wolpe S. D., Wilkie N. M., Donaldson D., et al. (1990) Identification and characterization of an inhibitor of haemopoietic stem cell proliferation. Nature 344, 442–444.

    Article  PubMed  CAS  Google Scholar 

  28. Nagasawa T., Hirota S., Tachibana K., Takaura N., Nishikawa S., Kitamura Y., et al. (1996) Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382, 635–638.

    Article  PubMed  CAS  Google Scholar 

  29. Sarris A. H., Broxmeyer H. E., Wirthmueller U., Karasavvas N., Cooper S., Lu L., et al. (1993) Human interferon-inducible protein 10: expression and purification of recombinant protein demonstrate inhibition of early human hematopoietic progenitors. J. Exp. Med. 178, 1127–1132.

    Article  PubMed  CAS  Google Scholar 

  30. Karpus W. J. and Kennedy K. J. (1997) MIP-1 alpha and MCP-1 differentially regulate acute and relapsing autoimmune encephalomyelitis as well as Th1/Th2 lymphocyte differentiation. J. Leukoc. Biol. 62, 681–687.

    PubMed  CAS  Google Scholar 

  31. Van Snick J., Houssiau F., Proost P., Van Damme J., and Renauld J. C. (1996) I-309/T cell activation gene 3 chemokine protects murine T cell lymphomas against dexamethasone induced apoptosis. J. Immunol. 157, 2570–2576.

    PubMed  Google Scholar 

  32. Cook D. N., Beck M. A., Coffman T. M., Kirby S. L., Sheridan J. F., Pragnell I. B., and Smithies O. (1995) Requirement of MlP-1α for an inflammatory response to viral infection. Science 269, 1583–1585.

    Article  PubMed  CAS  Google Scholar 

  33. Cocchi F., DeVico A. L., Garzino-Demo A., Arya S. K., Gallo R. C., and Lusso P. (1995) Identification of RANTES, MlP-lα, and MIP-1 β as the major HIV-suppressive factors produced by CD8+ T cells. Science 270, 1811–1815.

    Article  PubMed  CAS  Google Scholar 

  34. Xia M., Qin S., McNamara M., Mackay C., and Hyman B. J. (1997) Interleukin-8 receptor B immunoreactivity in brain and neuritic plaques of Alzheimer’s disease. Am. J. Path. 150, 1267–1274.

    PubMed  CAS  Google Scholar 

  35. Gupta S. K., Lysko P. G., Pillarisetti K., Ohlstei E., and Stadel J. M. (1998) Chemokine receptors in human endothelial cells. Functional expression of CXCR4 and its transcriptional regulation by inflammatory cytokines. J. Biol. Chem. 273, 4282–4287.

    Article  PubMed  CAS  Google Scholar 

  36. Chuntharapai A., Lee J., Burnier J., Wood W. I., Hebert C., and Kim K. J. (1994) Neutralizing monoclonal antibodies to human IL-8 receptor A map to the NH2-terminal region of the receptor. J. Immunol. 152, 1783–1789.

    PubMed  CAS  Google Scholar 

  37. Chuntharapai A., Lee J., Hebert C. A., and Kim K. J. (1994) Monoclonal antibodies detect different distribution patterns of IL-8 receptor A and IL-8 receptor B on human peripheral blood leukocytes. J. Immunol. 153, 5682–5688.

    PubMed  CAS  Google Scholar 

  38. Endres M. J., Clapham P. R., Marsh M., Ahuja M., Turner J. D., McKnight A., Thomas J. F., Stoebenau-Haggarty B., Choe S., Vance P. J., Wells T. N. C., Power C. A., Sutterwala S. S., Doms R. W., Landau N. R., and Hoxie J. A. (1996) CD4-independent infection by HIV-2 is mediated by fusin/CXCR4. Cell 87, 745–756.

    Article  PubMed  CAS  Google Scholar 

  39. Forster R., Emrich T., Kremmer E., and Lipp M. (1994) Expression of the G-protein-coupled receptor BLR1 defines mature, recirculating B cells and a subset of T-helper memory cells. Blood 84, 830–840.

    PubMed  CAS  Google Scholar 

  40. Frade J. M. R., Llorente M., Mellado M., Alcami J., Gutierrez-Ramos J. C., Zaballos A., del Real G., and Martinez-A. C. (1997) The amino-terminal domain of the CCR2 chemokine receptor acts as a coreceptor for HIV-1 infection. J. Clin. Invest. 100, 497–502.

    Article  PubMed  CAS  Google Scholar 

  41. Wu L., Paxton W. A., Kassam N., Ruffing N., Rottman J. B., Sulliva N., et al. (1997) CCR5 levels and expression pattern correlate with infectability by mac-rophage-tropic HIV-1, in vitro. J. Exp. Med 185, 1681–1691.

    Article  PubMed  CAS  Google Scholar 

  42. Wu L., LaRosa G., Kassa N., Gordon C. J., Heath H., Ruffing N., et al. (1997) Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding. J. Exp. Med. 186, 1373–1381.

    Article  PubMed  CAS  Google Scholar 

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Ponath, P.D., Kassam, N., Qin, S. (2000). Monoclonal Antibodies to Chemokine Receptors. In: Proudfoot, A.E.I., Wells, T.N.C., Power, C.A. (eds) Chemokine Protocols. Methods in Molecular Biology, vol 138. Humana Press. https://doi.org/10.1385/1-59259-058-6:231

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  • DOI: https://doi.org/10.1385/1-59259-058-6:231

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-722-9

  • Online ISBN: 978-1-59259-058-2

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