Skip to main content
SpringerLink
Log in

Chemokines and their role in disease

  • Review
  • Published:
International Journal of Clinical and Laboratory Research

Abstract

Chemokines appear to play a role in disease progression at multiple levels. They originally were described as mediators of leukocyte recruitment and activation. However, recent evidence suggests that they can also alter the outcome of the immune response by altering the cytokine profile of a response. The true nature of the influence that chemokines have upon a particular response and the identification of critical chemokines as therapeutic targets can only be determined by thorough analysis of appropriate responses in animal models. Because of the diversity of chemokine production, the number and type of chemokines, and the permiscuous binding pattern for multiple receptors, the identification and elucidation of mechanisms will be difficult. Future studies into the function of chemokines should investigate the specific functions of individual chemokines during various phases of disease. Only then can their true functions be elucidated.

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. Imhof BA, Dunon D. Leukocyte migration and adhesion. Adv Immunol 1995; 58:345.

    Article  PubMed  CAS  Google Scholar 

  2. Springer TA, Dustin ML, Kishimoto TK, Martin SD. The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol 1987; 5:223.

    Article  PubMed  CAS  Google Scholar 

  3. Witt DP, Lander AD. Differential binding of chemokines to glycosaminoglycan subpopulations. Curr Biol 1994; 1:394.

    Article  Google Scholar 

  4. Schall TJ. Biology of the RANTES/SIS cytokine family. Cytokine 1991; 3:165.

    Article  PubMed  CAS  Google Scholar 

  5. Kunkel SL, Strieter RM, Lindley IJ, Westwick J. Chemokines: new ligands, receptors and activities. Immunol Today 1995; 16:559.

    Article  PubMed  CAS  Google Scholar 

  6. Bacon KB, Premack BA, Gardner P, Schall TJ. Activation of dual T cell signaling pathways by the chemokine RANTES. Science 1995; 269:1727.

    Article  PubMed  CAS  Google Scholar 

  7. Lukacs NW, Chensue SW, Keefer C, Karpus WJ, Strieter RM, Kunkel SL. C-C chemokines differentially alter IL-4 production from lymphocytes. Am J Pathol 1997; 150:1861.

    PubMed  CAS  Google Scholar 

  8. Karpus WJ, Lukacs NW, Kennedy KJ, Smith WS, Hurst SD, Barrett TA. Differential C-C chemokine-induced potentiation of Th cell cytokine production. J Immunol 1997; 158:4129.

    PubMed  CAS  Google Scholar 

  9. Hogaboam CM, Lukacs NW, Strieter RM, Kunkel SL. Monocyte chemoattractant protein-1 synthesis by lung fibroblasts modulates T cell activation. J Immunol. In press.

  10. Zisman DA, Kunkel SL, Strieter RM, Tsai WC, Bucknell K, Wilkowski J, Standiford TJ. MCP-1 protects mice in lethal endotoxemia. J Clin Invest 1997; 99:2832.

    Article  PubMed  CAS  Google Scholar 

  11. Neote K, DiGregorio D, Mak JY, Horuk R, Schall TJ. Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor. Cell 1993; 72:415.

    Article  PubMed  CAS  Google Scholar 

  12. Charo IF Myers SJ, Herman A, Franci C, Connolly AJ, Coughlin SR. Molecular cloning and functional expression of two monocyte chemoattractant protein-1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc Natl Acad Sci USA 1994; 91:2752.

    Article  PubMed  CAS  Google Scholar 

  13. Post TW, Bozic CR, Rothenberg ME, Luster AD, Gerard N, Gerard C. Molecular characterization of two murine eosinophil b chemokine receptors. J Immunol 1995; 155:5299.

    PubMed  CAS  Google Scholar 

  14. Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Pamentier SC, Collman RG, Doms RW. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKRR-5, CKR-3, and CDR2b as fusion cofactors. Cell 1996; 85:1149.

    Article  PubMed  CAS  Google Scholar 

  15. Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard C, Sodroski J. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 1996; 85:1135.

    Article  PubMed  CAS  Google Scholar 

  16. Bleul CC, Farzan M, Choe H, Parolin C, Clarke-Lewis I, Sodroski J, Springer TA. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 1996; 382:829.

    Article  PubMed  CAS  Google Scholar 

  17. Mackewicz CE, Barker E, Greco G, Reyes-Teran G, Levy JA. Do beta-chemokines have clinical relevance in HIV infection? J Clin Invest 1997; 100:921.

    Article  PubMed  CAS  Google Scholar 

  18. Sozzani S, Luini W, Boratti A, Polentarutti N, Zhou D, Piedmonti L, D’Amico G, Power CA, Wells TN, Gobbi M, Allavena P, Mantovani A. Receptor expression and responsiveness of human dendritic cells to a defined set of C-C and C-x-C chemokines. J Immunol 1998; 159:1993.

    Google Scholar 

  19. Gao JL, Murphy PM. Human cytomegalovirus open reading frame US28 encodes a functional beta chemokine receptor. J Biol Chem 1994; 269:28539.

    PubMed  CAS  Google Scholar 

  20. Smith CA, Smith TD, Smolad PJ, Friend D, Hagen H, Gerhart M, Park L, Pickup DJ, Torrance D, Mohler K, Schooley K, Goodwin RG. Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors. Virology 1997; 236:316.

    Article  PubMed  CAS  Google Scholar 

  21. Fujishima S, Sasaki J, Shinozawa Y, Kimura K, Suzuki M, Kanazawa M, Hori S, Aikawa N. Serum MIP-1α and IL-8 in septic patients. Intensive Care Med 1996; 22:1169.

    Article  PubMed  CAS  Google Scholar 

  22. Standiford TJ, Strieter RM, Lukacs NW, Kunkel SL. Neutralization of IL-10 increases lethality in endotoxemia: cooperative effects of macrophage inflammatory protein-2 and tumor necrosis factor. J Immunol 1995; 155:2222.

    PubMed  CAS  Google Scholar 

  23. Shanley TP, Schmal H, Friedl HP, Jones ML, Ward PA. Role of macrophage inflammatory protein-1α (MIP-1α) in acute lung injury in rats. J Immunol 1991; 154:4793.

    Google Scholar 

  24. Standiford TJ, Kunkel SL, Lukacs NW, Greenberger MJ, Danforth JM, Kunkel RG, Strieter RM. Macrophage inflammatory protein-1a mediates lung leukocyte recruitment, lung capillary leak, and early mortality in murine endotoxemia. J Immunol 1995; 155:1515.

    PubMed  CAS  Google Scholar 

  25. Xing Z, Jordana M, Kirpalani H, Driscoll KE, Schall TJ, Gauldie J. Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-a, macrophage inflammatory protein-2, interleukin-1b, and interleukin-6 but not RANTES or transforming growth factor-b1 mRNA expression in acute lung inflammation. Am J Respir Cell Mol Biol 1994; 10:148.

    PubMed  CAS  Google Scholar 

  26. Van Otteren GM, Strieter RM, Kunkel SL, Paine R, Greenberger MJ, Danforth JM, Burdick MD, Standiford TJ. Compartmentalized expression of RANTES in a murine model of endotoxemia. J Immunol 1995; 154: 1900.

    Google Scholar 

  27. Brusselle G, Kips J, Joos G, Bluethmann H, Pauwels R. Allergen-induced airway inflammation and bronchial responsiveness in wild-type and interleukin-4-deficient mice. Am J Respir Cell Mol Biol 1995; 12:254.

    PubMed  CAS  Google Scholar 

  28. Brusselle GG, Kips JC, Tavernier JH, Heyden JG van der, Cuvelier CA, Pauwels RA, Bluethmann H. Atttenuation of allergic airway inflammation in IL-4 deficient mice. Clin Exp Allergy 1994; 24:73.

    Article  PubMed  CAS  Google Scholar 

  29. Van Oosterhout AJ, Ladenius AR, Savelkroul HF, Van Ark I, Delsman KC, Nijkamp FP. Effect of anti-IL-5 and IL-5 on airway hyperreactivity and eosinophils in guinea pigs. Am Rev Resp Dis 1993; 147:548.

    PubMed  Google Scholar 

  30. Jose PJ, Griffiths-Johnson DA, Collins PD, Walsh DT, Moqbel R, Totty NF, Truong O, Hsuan JJ, Williams TJ. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med 1994; 179:881.

    Article  PubMed  CAS  Google Scholar 

  31. MacLean JA, Ownbey R, Luster AD. T cell-dependent regulation of eotaxin in antigen-induced pulmonary eosinophilia. J Exp Med 1996; 184: 1461.

    Article  PubMed  CAS  Google Scholar 

  32. Rothenberg ME, Ownby R, Mehlhop PD, Loiselle PM, Rijn M van de, Bonventre JV, Oettgen HC, Leder P, Luster AD. 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; 2:334.

    PubMed  CAS  Google Scholar 

  33. Lukacs NW, Strieter RM, Chensue SW, Kunkel SL. Interleukin-4-dependent pulmonary eosinophil infiltration in a murine model of asthma. Am J Respir Cell Mol Biol 1994; 10:526.

    PubMed  CAS  Google Scholar 

  34. Lukacs NW, Strieter RM, Chensue SW, Widmer M, Kunkel SL. TNFa mediates recruitment of neutrophils and eosinophils during airway inflammation. J Immunol 1994; 154:5411.

    Google Scholar 

  35. Lukacs NW, Standiford TJ, Strieter RM, Chensue SW, Kunkel RG, Kunkel SL. C-C chemokine-induced eosinophil chemotaxis during allergic airway inflammation. J Leukoc Biol 1996; 60: 573.

    PubMed  CAS  Google Scholar 

  36. Lukacs NW, Strieter RM, Warmington K, Lincoln P, Chensue SW, Kunkel SL. Differential recruitment of leukocyte populations and alteration of airway hyperreactivity by C-C family chemokines in murine allergic airway inflammation. J Immunol 1997; 158:4398.

    PubMed  CAS  Google Scholar 

  37. Conti P, Boucher W, Letourneau R, Feliciani C, Reale M, Barbacane RC, Vlagopoulos P, Bruneau G, Thibault J, Theoharides TC. Monocyte chemotactic protein-1 provokes mast cell aggregation and [3H]5HT release. Immunology 1995; 86:434.

    PubMed  CAS  Google Scholar 

  38. Kuna P, Reddigari SR, Rucinski D, Oppenheim JJ, Kaplan A. Monocyte chemotactic and activating factor is a potent histamine-releasing factor for human basophils. J Exp Med 1992; 175:489.

    Article  PubMed  CAS  Google Scholar 

  39. Tuohy VK, Sobel RA, Lu Z, Laursen RA, Lees MB. Myelin proteolipid protein: minimum sequence requirements for active induction of autoimmune encephalomyelitis in SWR/J and SJL/J mice. J Neuroimmunol 1992; 39:67.

    Article  PubMed  CAS  Google Scholar 

  40. Karpus WJ, Lukacs NW, McRae BL, Strieter RM, Kunkel SL, Miller SD. An essential role for chemokines in the pathogenesis of T cell-mediated autoimmune disease. J Immunol 1995; 155:5003.

    PubMed  CAS  Google Scholar 

  41. Calvo CF, Yoshimura T, Gelman M, Mallat M. Production of monocyte chemotactic protein-1 by rat brain macrophages. Eur J Neurosci 1996; 8: 1725.

    Article  PubMed  CAS  Google Scholar 

  42. Glabinski AR, Tani M, Tuohy VK, Tuthill RJ, Ransohoff RM. Central nervous system chemokine mRNA accumulation follows initial leukocyte entry at the onset of acute murine experimental autoimmune encephalomyelitis. Brain Behav Immun 1995; 9:315.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Michigan Medical School, 1301 Catherine, 48109-0602, Ann Arbor, Michigan, USA

    N. W. Lukacs & S. L. Kunkel

Authors
  1. N. W. Lukacs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. L. Kunkel
    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

Lukacs, N.W., Kunkel, S.L. Chemokines and their role in disease. Int J Clin Lab Res 28, 91–95 (1998). https://doi.org/10.1007/s005990050025

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s005990050025

Key words

Search

Navigation