Neurochemical Research

, Volume 21, Issue 4, pp 481–487 | Cite as

Receptor-mediated phagocytosis of myelin by macrophages and microglia: Effect of opsonization and receptor blocking agents

  • K. Mosley
  • M. L. Cuzner
Original Articles

Abstract

Myelin is phagocytosed by microglia (MG) and to a somewhat lesser extent by peritoneal macrophages (Mϕ) in a dose- and time-dependent manner. In serum-free medium opsonization of rat myelin significantly enhances binding and ingestion, more by rat macrophages than by microglia. Furthermore the requirement for opsonization is not restricted to anti-myelin antibodies as the difference in the rate of myelin uptake by macrophages is largely eliminated when they are cultured in 10% fetal calf serum. Binding and ingestion of both myelin and opsonized myelin are inhibited to the same dose-dependent extent by zymosan, oxidized LDL, peroxidase-antiperoxidase (PAP), opsonized erythrocytes and the anti-CR3 antibody OX42 implicating lectin, scavenger, Fc and complement receptors in the phagocytosis of myelin. Thus while the differential uptake of myelin and opsonized myelin by macrophages would indicate a central role for the Fc receptor, binding inhibition studies implicate a range of membrane receptors which would obviate the need for antigen-antibody complexing to stimulate phagocytosis. Uptake of both myelin preparations by macrophages or microglia is stimulated by interferon-γ and inhibited by TGF-β, and the process of ingestion results in increased nitric oxide release and decreased superoxide production, the effect being more pronounced when myelin is opsonized.

Key Words

Myelin microglia macrophages free radicals zymosan CR3 cytokines 

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References

  1. 1.
    Cuzner, M. L., Hayes, G. M., Newcombe, J., and Woodroofe, M. N. 1988. The nature of inflammatory components during demyelination in multiple sclerosis. Journal of Neuroimmunol 20:203–209.CrossRefGoogle Scholar
  2. 2.
    Goldenberg, P. Z., Kwon, E. E., Benjamins, J. A., Whitaker, J. N., Quarles, R. H., and Prineas, J. W. 1989. Opsonization of normal myelin by anti-myelin antibodies and normal serum. J. Neuroimmunol. 23:157–166.PubMedCrossRefGoogle Scholar
  3. 3.
    Trotter, J., DeJong, L. D., and Smith, M. E. 1986. Opsonization with antimyelin antibody increases the uptake and intracellular metabolism of myelin in inflammatory macrophages. J. Neurochem. 47:779–789.PubMedCrossRefGoogle Scholar
  4. 4.
    Smith, M. E. 1993. Phagocytosis of myelin by microglia in vitro. J. Neurosci. Res. 35:480–487.PubMedCrossRefGoogle Scholar
  5. 5.
    Williams, K., Ulvestad, E., Waage, A., Antel, J. P., and Mclaurin, J. 1994. Activation of adult human derived microglia by myelin phagocytosis in vitro. J. Neurosci. Res. 38:433–443.PubMedCrossRefGoogle Scholar
  6. 6.
    Norton, W. T., and Cammer, W. 1984. Chemical pathology of disease involving myelin. In: Pages 369–403, Morrell, P. (ed) In “Myelin”. Plenum, New York.Google Scholar
  7. 7.
    Hayes, G. M., Woodroofe, M. N., and Cuzner, M. L. 1988. Characterization of microglia isolated from adult human and rat-brain. J. Neuroimmunol. 19:177–189.PubMedCrossRefGoogle Scholar
  8. 8.
    Ding, A. H., Nathan, C. F., and Stuehr, D. J. 1988. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J. Immunol. 141:2407–2412.PubMedGoogle Scholar
  9. 9.
    Pick, E., and Mizel, D. 1981. Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J. Immunol. Meth. 46:211–216.CrossRefGoogle Scholar
  10. 10.
    Loughlin, A. J., Woodroofe, M. N., and Cuzner, M. L. 1992. Regulation of Fc receptor and major histocompatibility complex antigen expression on isolated rat microglia by tumor-necrosis-factor, interleukin-1 and lipopolysaccharide—effects on interferon-gamma induced activation. Immunology 75:170–175.PubMedGoogle Scholar
  11. 11.
    Krieger, M., Acton, S., Ashkenas, J., Pearson, A., Penman, M., and Resnick, D. 1993. Molecular flypaper, host defense, and atherosclerosis. J. Biol. Chem. 268:4569–4572.PubMedGoogle Scholar
  12. 12.
    Endemann, G., Stanton, L. W., Madden, K. S., Bryant, C. M., White, R. T., and Protter, A. A. 1993. CD 36 is a receptor for oxidized low density lipoprotein. J. Biol. Chem. 268:11811–11816.PubMedGoogle Scholar
  13. 13.
    Streit, W. J. and Kreutzberg, G. W. 1987. Lectin binding by resting and reactive microglia. J. Neurocytol. 16:249–260.PubMedCrossRefGoogle Scholar
  14. 14.
    Schreiber, S., Perkins, S. L., Teitelbaum, S. L., Chappel, J., Stahl, P. D., and Blum, J. S. 1993. Regulation of mouse bone marrow macrophage mannose receptor expression and activation by protaglandin E and IFN-γ1. J. Immunol. 151:4973–4981.PubMedGoogle Scholar
  15. 15.
    Kimberly, R. P., Tappe, N. J., Merriam, L. T., Redecha, P. B., Eddberg, J. C., Schwartzman, S., and Valinsky, J. E. 1989. Carbohydrates on human Fc receptors. J. Immunol. 142:3923–3930.PubMedGoogle Scholar
  16. 16.
    Sanguedolce, M. V., Capo, C., Bouhamadan, M., Bongrand, P., Huang, C. K., and Mege, J. L. 1992. Zymosan induced tyrosine phosphorylations in human monocytes. J. Immunol. 151:405–414.Google Scholar
  17. 17.
    Aramaki, Y., Murai, M., and Tsuchiya, S. 1993. Contribution of N-acetyl-β-D-galactosamine-specific lectin to Fc receptor-mediated phagocytosis by mouse peritoneal macrophages. Immunology 79:403–407.PubMedGoogle Scholar
  18. 18.
    Ulvestad, E., Williams, K., Vedeler, C., Antel, J., Nyland, H., Mork, S., and Matre, R. 1994. Reactive microglia in multiple sclerosis lesions have an increased expression of receptors for the Fc part of IgG. J. Neurol. Sci. 121:125–131.PubMedCrossRefGoogle Scholar
  19. 19.
    Loughlin, A. J., Woodroofe, M. N., and Cuzner, M. L. 1993. Modulation of interferon-gamma-induced major histocompatibility complex class-11 and Fc-receptor expression on isolated microglia by transforming growth-factor-beta-1, interleukin-4, noradrenaline and glucocorticoids. Immunology 79:125–130.PubMedGoogle Scholar
  20. 20.
    Corradi, S. B., Buchmuller-Rouller, Y., and Mauel, J. 1991. Phagocytosis enhances murine macrophage activation by interferon-and tumor necrosis factor-α. Eur. J. Immunol. 21:2553–2558.Google Scholar
  21. 21.
    Fabian, R. H., and Rea, H. C. 1993. Neuronal toxicity by macrophages in mixed braincell culture is augmented by antineuronal IgG and dependent upon nitric oxide synthesis. J. Neuroimmunol. 44:95–102.PubMedCrossRefGoogle Scholar
  22. 22.
    Loegering, D. J., and Schwacha, M. G. 1991. Macrophage hydrogen peroxide production and phagocytic function are decreased following phagocytosis mediated by Fc receptors but not complement receptors. Biochem Biophys Res Commun 180:26–272.CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • K. Mosley
    • 1
  • M. L. Cuzner
    • 1
  1. 1.Multiple Sclerosis LaboratoryInstitute of NeurologyLondonUK

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