Skip to main content
SpringerLink
Log in

Response of Chemokine Antagonists to Inflammation in Injured Spinal Cord

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Inflammation is a primary reaction to infection, allergic disorders, autoimmune diseases, and mechanical injury. The goal of an inflammatory response is to rapidly respond to noxious stimuli, such as trauma or pathogen, with a controlled amplification of cellular activation to eliminate, control, or wall off the triggering agent. Although the inflammatory response is necessary for resolution of the pathogenic event, by stander or collateral tissue damage is caused by the toxic nature of many of its by-products. It is characterized by the infiltration of leukocytes into the affected area. Chemokines and their receptors play an essential role as mediators of leukocyte infiltration. In most cases this response is so vigorous that its control, especially in the central nervous system, would inhibit recovery. The benefits of anti-inflammatory therapy based on interference with the chemokine system has been established in animal models and is being pursued with chemokine antibodies and receptor antagonists. Prolonged treatment with a broad-spectrum chemokine antagonist, vMIPII, has been shown to reduce the rate of infiltration of monocytes into injured rat spinal cord and promote survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Baggiolini, M. 1998. Chemokines and leukocyte traffic. Nature 392:565–568.

    Google Scholar 

  2. Howard, O. M. Z., Oppenheim, J. J., and Wang, J. M. 1999. Chemokines as molecular targets for therapeutic intervention. J. Clinical Immunol. 19:280–292.

    Google Scholar 

  3. Huang, D., Han, Y., Sandhya Rani, M. R., Glabinski, A., Trebst, C., Sorensen, T., Tani, M., Wang, J., Chien, P., O'Bryan, S., Bielecki, B., Zhou, Z. L., Majumder, S., and Ransohoff, R. M. 2000. Chemokines and chemokine receptors in inflammation of the nervous system: Manifold roles and exquisite regulation. Immunol. Rev. 177:52–67.

    Google Scholar 

  4. Proudfoot, A. E. I., Power, C. A., and Wells, T. N. C. 2000. The strategy of blocking the chemokine system to combat disease. Immunol. Rev. 177:246–256.

    Google Scholar 

  5. Anthony, D. C., Blond, D., Dempster, R., and Perry, V. H. 2001. Chemokine targets in acute brain injury and disease. Prog. Brain Res. 132:507–524.

    Google Scholar 

  6. Baggiolini, M. 2001. Chemokines in pathology and medicine. J. Intern. Med. 250:91–104.

    Google Scholar 

  7. Bajetto, A., Bonavia, R., Barbero, S., Florio, T., and Schettini, G. 2001. Chemokines and their receptors in the central nervous system. Frontiers Neuroendocrinol. 22:147–184.

    Google Scholar 

  8. DeGroot, C. J. A. and Woodroofe, M. N. 2001. The role of chemokine receptors in CNS inflammation. Progr. in Brain Res. 132:533–544.

    Google Scholar 

  9. Gerard, C. and Rollins, B. J. 2001. Chemokines and disease. Nature Immunol. 2:108–115.

    Google Scholar 

  10. Horuk, R. 2001. Survey chemokine receptors. Cytokine Growth Factor Rev. 12:313–335.

    Google Scholar 

  11. Mackay, C. R. 2001. Chemokines: Immunology's high impact factors. Nature Immunol. 2:95–101.

    Google Scholar 

  12. Strieter, M., Standiford, T. J., Huffnagle, G. B., Colletti, L. M., Lukacs, N. W., and Kunkel, S. L. 1996. “The good, the bad, and the ugly”: The role of chemokines in models of human disease. J. Immunol. 156:3583–3586.

    Google Scholar 

  13. Sekido, N., Mukaida, N., Harada, A., Nakanishi, X., Watanabe, Y., and Matsushima, K. 1993. Prevention of lung perfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature 365:654–657.

    Google Scholar 

  14. Nishimura, A., Akahoshi, T., Takahashi, M., Takagishi, K., Itoman, M., Kondo, H., Takahashi, Y., Mukaida, N., and Matsushima, K. 1997. Attenuation of monosodium urate crystal-induced arthritis in rabbits by a neutralizing antibody against interleukin-8. J. Leukocyte Biol. 62:444–449.

    Google Scholar 

  15. Feng, L., Xia, Y., Yoshimura, T., and Wilson C. B. 1995. Modulation of neutrophil influx in glomerulonephritis in the rat with anti-macrophage inflammatory protein-2 (MIP-2) antibody. J. Clin. Invest. 95:1009–1017.

    Google Scholar 

  16. 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. Pathol. 148:855–864.

    Google Scholar 

  17. Lukacs, N. W., Streiter, R. M., Warmington, K., Lincoln, P., Chensue, S. W., and Kunkel, S. L. 1997. Differential recruitment of leukocyte populations and alteration of airway hyperreactivity by C-C family chemokines in allergic airway inflammation. J. Immunol. 158:4398–4404.

    Google Scholar 

  18. 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-1pr mouse model. J. Exp. Med. 186:131–137.

    Google Scholar 

  19. Plater-Zyberk, C., Hoogeewerf, A. J., Proudfoot, A. E. I., Power, C. A., and Wells, T. N. C. 1977. Effect of CC chemokine receptor antagonist on collagen induced arthritis in DBA/I mice. Immunol. Lett. 57:117–120.

    Google Scholar 

  20. Zhou, N., Luo, Z., Hall, J. W., and Huang, Z. 2000. A novel peptide antagonist of CXCR4 derived from the N-terminus of viral chemokine vMIPII. Biochemistry 39:3782–3787.

    Google Scholar 

  21. Gao, J. L. and Murphy, P. M. 1994. Human cytomegalovirus open reading frame US28 encodes a functional beta chemokine receptor. J. Biol. Chem. 269:28539–28542.

    Google Scholar 

  22. Ahuja, S. K. and Murphy, P. M. 1993. Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. J. Biol. Chem. 268:20691–20694.

    Google Scholar 

  23. Ahuja, S. K., Gao, J. L., and Murphy, P. M. 1994. Chemokine receptor and molecular mimicry. Immunol. Today 15:281–287.

    Google Scholar 

  24. Murayama, T., Kuno, K., Jisaki, F., Obuchi, M., Sakamuro, D., Furukawa, T., Mukaida, N., and Matsushima, K. (1994) Enhancement human cytogalovirus replication in a human lung fibroblast cell line by interleukin-8. J. Virol. 68:7582–7585.

    Google Scholar 

  25. Alcami, A., Symons, J. A., Collins, P. D., Williams, T. J., and Smith, G. L. 1998. Blockade of chemokine activity by a soluble chemokine binding protein from vaccinia virus. J. Immunol. 160:624–633.

    Google Scholar 

  26. Anderson, D. K. 1992. Chemical and cellular mediators in spinal cord injury. J. Neurotrauma. 9:143–145; discussion 145–146.

    Google Scholar 

  27. Faden, A. I. 1996. Pharmacological treatment of central nervous system trauma. Pharmacol. Toxicol. 78:12–7.

    Google Scholar 

  28. Martiney, J. A., Cuff, C., Litwak, M., Berman, J., and Brosnan, C. F. 1998. Cytokine-induced inflammation in the central nervous system revisited. Neurochem. Res. 23:349–359.

    Google Scholar 

  29. Hayashi, M., Ueyama, T., Tamaki, T., and Senba, E. 1997. Expression of neurotrophin and IL-1 beta mRNAs following spinal cord injury and the effects of methylprednisolone treatment. Kaibogaku Zasshi. J. Anat. 72:209–213.

    Google Scholar 

  30. Ichitani, Y., Shi, T., Haeggstrom, J. Z., Samuelsson, B., and Hokfelt, T. 1997. Increased levels of cyclooxygenase-2 mRNA in the rat spinal cord after peripheral inflammation: An in situ hybridization study. Neuroreport 8(13):2949–2952.

    Google Scholar 

  31. Yong, V. W. 1996. Cytokines: Astrogliosis and neurotrophism following CNS trauma. Page 309, In Cytokines and the CNS, R. M. Ransohoff and E. N. Benveniste (eds), CRC Press Inc. Boca Raton, Florida.

    Google Scholar 

  32. Eng, L. F., Ghirnikar, R. S., and Lee, Y. L. 1996. Inflammation in EAE: Role of chemokine/cytokine expression by resident and infiltrating cells. Neurochem. Res. 21:511–525.

    Google Scholar 

  33. Ghirnikar, R. S., Lee, Y. L., and Eng, L. F. 1998. Inflammation in traumatic brain injury: Role of cytokines and chemokines. Neurochem. Res. 23:329–340.

    Google Scholar 

  34. Dong, Y. and Benveniste, E. N. 2001. Immune function of astrocytes. Glia. 36:180–190.

    Google Scholar 

  35. Hausmann, E. H. S., Berman, N. E. J., Wang, Y.-Y., Meara, J. B., Wood, G. W., and Klein, R. M. 1998. Selective chemokine mRNA expression following brain injury. Brain Res. 788:49–59.

    Google Scholar 

  36. Baggiolini, M. 2000. Reflection on chemokines. Immunol. Rev. 177:5–7.

    Google Scholar 

  37. Boring, L., Gosling, J., Chensue, S. W., Kunkel, S. L., Farese, R. V., Jr., Broxmeyer, H. E., and Charo, I. F. 1997. Impaired monocyte migration and reduced type 1 (Th1) cytokine response in C-C chemokine receptor 2 knockout mice. J. Clin. Invest. 100:2552–2561.

    Google Scholar 

  38. Boring, L., Gosling, J., Cleary, M., and Charo, I. F. 1998. Decreased lesion formation in CCR2-/-mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394: 894–897.

    Google Scholar 

  39. Kurihara, T., Warr, G., Loy, J., and Bravo, R. 1997. Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J. Exp. Med. 186:1757–1762.

    Google Scholar 

  40. Kuziel, W. A., Morgan, S. J., Dawson, T. C., Griffin, S., Smithies, O., Ley, K., and Maeda, N. 1997. Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc. Nat. Acad. Sci. U.S.A. 94:12053–12058.

    Google Scholar 

  41. Fife, B. T., Huffnagle, G. B., Kuziel, W. A., and Karpus, W. J. 2000. CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J. Exp. Med. 192: 899–905.

    Google Scholar 

  42. Izikson, L., Klein, R. S., Charo, I. F., Weiner, H. L., and Luster, A. D. 2000. Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J. Exp. Med. 192:1075–1080.

    Google Scholar 

  43. Ghirnikar, R. S., Lee, Y. L., LiJ. D., and Eng, L. F. 1998. Chemokine inhibition in rat stab wound brain injury using antisense oligodeoxynucleotides. Neurosci. Lttr. 247:21–14.

    Google Scholar 

  44. Popovich P., Wei P., Stokes B. T. 1997. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J. Comp. Neurol. 377:443–464.

    Google Scholar 

  45. McTigue, D. M., Tani, M., Krivacic, K., Chernosky, A., Kelner, G. S., Maciejewski, D., Maki, R., Ransohoff, R. M., and Stokes, B. T. 1998. Selective chemokine mRNA accumulation in the rat spinal cord after contusion injury. J. Neurosci. Res. 53:368–376.

    Google Scholar 

  46. Lee, Y. L., Shih, K., Bao, P., Ghirnikar, R. S., and Eng, L. F. 2000. Cytokine/chemokine expression in contused rat spinal cord. Neurochem. Intl. 36:417–425.

    Google Scholar 

  47. Ghirnikar, R. S., Lee, Y. L., and Eng, L. F. 2000. Chemokine antagonist infusion attenuates cellular infiltration following contusion injury in rat. J. Neurosci. Res. 59:63–73.

    Google Scholar 

  48. Ghirnikar, R. S., Lee, Y. L., and Eng, L. F. 2001. Chemokine antagonist infusion promotes axonal sparing following spinal cord contiusion injury in rat. J. Neurosci. Res. 64:582–589.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pathology and Laboratory Medicine Service (113), VAPA Health Care System, Palo Alto, California

    Lawrence F. Eng & Yuen Ling Lee

Authors
  1. Lawrence F. Eng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuen Ling Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lawrence F. Eng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eng, L.F., Lee, Y.L. Response of Chemokine Antagonists to Inflammation in Injured Spinal Cord. Neurochem Res 28, 95–100 (2003). https://doi.org/10.1023/A:1021652229667

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021652229667

Search

Navigation