Journal of Molecular Neuroscience

, Volume 39, Issue 1–2, pp 99–103

The Role of Galectin-3/MAC-2 in the Activation of the Innate-Immune Function of Phagocytosis in Microglia in Injury and Disease



Microglia are a self-sustained population of immune/myeloid cells present throughout the central nervous system (CNS). Microglia are in a “resting” state in the normal adult CNS. They turn “active” in injury and disease (e.g., trauma, neurodegeneration, and infection). Activated microglia can be beneficial as well as detrimental/neurotoxic. The innate-immune function of phagocytosis of tissue debris, neurotoxic factor, and pathogens is a beneficial function of microglia. The current manuscript reviews the role of Galectin-3 (known also as MAC-2; Galectin-3/MAC-2) in the activation of the phagocytosis of degenerated myelin that is mediated by complement receptor-3 (known also as MAC-1; CD11b/CD18; αMβ2 integrin) and SRA (scavenger receptor-AI/II). Observations suggest that Galectin-3/MAC-2 may act as a molecular switch that activates phagocytosis by up-regulating and prolonging KRas-GTP-dependent PI3K (phosphatidylinositol 3-kinase) activity. A similar mechanism may regulate the phagocytosis of other tissue debris, neurotoxic factors and pathogens in neurodegenerative and infectious diseases.


Galectin-3 MAC-2 Phagocytosis Wallerian degeneration Neurodegenetation Myelin 


  1. Ajami, B., Bennett, J. L., Krieger, C., Tetzlaff, W., & Rossi, F. M. (2007). Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nature Neuroscience, 10, 1538–1543.PubMedCrossRefGoogle Scholar
  2. Alliot, F., Godin, I., & Pessac, B. (1999). Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Developmental Brain Research, 117, 145–152.PubMedCrossRefGoogle Scholar
  3. Ashery, U., Yizhar, O., Rotblat, B., Elad-Sfadia, G., Barkan, B., Haklai, R., et al. (2006). Spatiotemporal organization of Ras signaling: Rasosomes and the Galectin switch. Cellular and Molecular Neurobiology, 26, 471–495.PubMedCrossRefGoogle Scholar
  4. Be'eri, H., Reichert, F., Saada, A., & Rotshenker, S. (1998). The cytokine network of Wallerian degeneration: IL-10 and GM-CSF. European Journal of Neuroscience, 10, 2707–2713.PubMedCrossRefGoogle Scholar
  5. Bell, M. D., Lopez-Gonzalez, R., Lawson, L., Hughes, D., Fraser, I., Gordon, S., et al. (1994). Upregulation of the macrophage scavenger receptor in response to different forms of injury in the CNS. Journal of Neurocytology, 23, 605–613.PubMedCrossRefGoogle Scholar
  6. Block, M. L., Zecca, L., & Hong, J. S. (2007). Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms. Nature Reviews Neuroscience, 8, 57–69.PubMedCrossRefGoogle Scholar
  7. Cohen, G., Makranz, C., Spira, M., Kodama, T., Reichert, F., & Rotshenker, S. (2006). Non-PKC DAG/Phorbol-Ester receptor(s) inhibit complement receptor-3 and nPKC inhibit scavenger receptor-AI/II-mediated myelin phagocytosis but cPKC, PI3K, and PLCgamma activate myelin phagocytosis by both. Glia, 53, 538–550.PubMedCrossRefGoogle Scholar
  8. Dumic, J., Dabelic, S., & Flogel, M. (2006). Galectin-3: An open-ended story. Biochimica Biophysica Acta, 1760, 616–635.Google Scholar
  9. Gao, H. M., & Hong, J. S. (2008). Why neurodegenerative diseases are progressive: Uncontrolled inflammation drives disease progression. Trends in Immunology, 29, 357–365.PubMedCrossRefGoogle Scholar
  10. Griffin, J. W., George, R., Lobato, C., Tyor, W. R., Yan, L. C., & Glass, J. D. (1992). Macrophage responses and myelin clearance during Wallerian degeneration: Relevance to immune-mediated demyelination. Journal of Neuroimmunology, 40, 153–165.PubMedCrossRefGoogle Scholar
  11. Hanisch, U. K., & Kettenmann, H. (2007). Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nature Neuroscience, 10, 1387–1394.PubMedCrossRefGoogle Scholar
  12. Hannila, S. S., Siddiq, M. M., & Filbin, M. T. (2007). Therapeutic approaches to promoting axonal regeneration in the adult mammalian spinal cord. International Review of Neurobiology, 77, 57–105.PubMedCrossRefGoogle Scholar
  13. Ho, M. K., & Springer, T. A. (1982). Mac-2, a novel 32,000 Mr mouse macrophage subpopulation-specific antigen defined by monoclonal antibodies. Journal of Immunology, 128, 1221–1228.Google Scholar
  14. Kotter, M. R., Li, W. W., Zhao, C., & Franklin, R. J. M. (2006). Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. Journal of Neuroscience, 26, 328–332.PubMedCrossRefGoogle Scholar
  15. Kreutzberg, G. W. (1996). Microglia: A sensor for pathological events in the CNS. Trends in Neurosciences, 19, 312–318.PubMedCrossRefGoogle Scholar
  16. Makranz, C., Cohen, G., Baron, A., Levidor, L., Kodama, T., Reichert, F., et al. (2004). Phosphatidylinositol 3-kinase, phosphoinositide-specific phospholipase-Cgamma and protein kinase-C signal myelin phagocytosis mediated by complement receptor-3 alone and combined with scavenger receptor-AI/II in macrophages. Neurobiology of Disease, 15, 279–286.PubMedCrossRefGoogle Scholar
  17. McKerracher, L., & David, S. (2004). Easing the brakes on spinal cord repair. Natural Medicines, 10, 1052–1053.CrossRefGoogle Scholar
  18. Mead, R. J., Singhrao, S. K., Neal, J. W., Lassmann, H., & Morgan, B. P. (2002). The membrane attack complex of complement causes severe demyelination associated with acute axonal injury. Journal of Immunology, 168, 458–465.Google Scholar
  19. Mildner, A., Schmidt, H., Nitsche, M., Merkler, D., Hanisch, U. K., Mack, M., et al. (2007). Microglia in the adult brain arise from Ly6ChiCCR2+ monocytes only under defined host conditions. Nature Neuroscience, 10, 1544–1553.PubMedCrossRefGoogle Scholar
  20. Perry, V. H., Brown, M. C., & Gordon, S. (1987). The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration. Journal of Experimental Medicine, 165, 1218–1223.PubMedCrossRefGoogle Scholar
  21. Reichert, F., & Rotshenker, S. (1996). Deficient activation of microglia during optic nerve degeneration. Journal of Neuroimmunology, 70, 153–161.PubMedCrossRefGoogle Scholar
  22. Reichert, F., & Rotshenker, S. (1999). Galectin-3/MAC-2 in experimental allergic encephalomyelitis. Experimental Neurology, 160, 508–514.PubMedCrossRefGoogle Scholar
  23. Reichert, F., & Rotshenker, S. (2003). Complement-receptor-3 and scavenger-receptor-AI/II mediated myelin phagocytosis in microglia and macrophages. Neurobiology of Disease, 12, 65–72.PubMedCrossRefGoogle Scholar
  24. Reichert, F., Saada, A., & Rotshenker, S. (1994). Peripheral nerve injury induces Schwann cells to express two macrophage phenotypes: Phagocytosis and the galactose-specific lectin MAC-2. Journal of Neuroscience, 14, 3231–3245.PubMedGoogle Scholar
  25. Reichert, F., Slobodov, U., Makranz, C., & Rotshenker, S. (2001). Modulation (inhibition and augmentation) of complement receptor-3-mediated myelin phagocytosis. Neurobiology of Disease, 8, 504–512.PubMedCrossRefGoogle Scholar
  26. Rinner, W. A., Bauer, J., Schmidts, M., Lassmann, H., & Hickey, W. F. (1995). Resident microglia and hematogenous macrophages as phagocytes in adoptively transferred experimental autoimmune encephalomyelitis: An investigation using rat radiation bone marrow chimeras. Glia, 14, 257–266.PubMedCrossRefGoogle Scholar
  27. Rio-Hortega, P. d. (1932). Microglia. In W. Penfield (Ed.), Cytology and cellular pathology of the nervous system (pp. 481–534). New York: Hafner.Google Scholar
  28. Rotshenker, S. (2003). Microglia and macrophage activation and the regulation of complement-receptor-3 (CR3/MAC-1)-mediated myelin phagocytosis in injury and disease. Journal of Molecular Neuroscience, 21, 65–72.PubMedCrossRefGoogle Scholar
  29. Rotshenker, S., Reichert, F., Gitik, M., Haklai, R., Elad-Sfadia, G., & Kloog, Y. (2008). Galectin3/MAC-2, Ras and PI3K activate complement receptor-3 and scavenger receptor-AI/II mediated myelin phagocytosis in microglia. Glia, 56, 1607–1613.PubMedCrossRefGoogle Scholar
  30. Saada, A., Reichert, F., & Rotshenker, S. (1996). Granulocyte macrophage colony stimulating factor produced in lesioned peripheral nerves induces the up-regulation of cell surface expression of MAC-2 by macrophages and Schwann cells. Journal of Cell Biology, 133, 159–167.PubMedCrossRefGoogle Scholar
  31. Silverman, B. A., Carney, D. F., Johnston, C. A., Vanguri, P., & Shin, M. L. (1984). Isolation of membrane attack complex of complement from myelin membranes treated with serum complement. Journal of Neurochemistry, 42, 1024–1029.PubMedCrossRefGoogle Scholar
  32. Skaper, S. D. (2007). The brain as a target for inflammatory processes and neuroprotective strategies. Annals of the New York Academy of Sciences, 1122, 23–34.PubMedCrossRefGoogle Scholar
  33. Slobodov, U., Reichert, F., Mirski, R., & Rotshenker, S. (2001). Distinct inflammatory stimuli induce different patterns of myelin phagocytosis and degradation in recruited macrophages. Experimental Neurology, 167, 401–409.PubMedCrossRefGoogle Scholar
  34. Smith, M. E. (2001). Phagocytic properties of microglia in vitro: Implications for a role in multiple sclerosis and EAE. Microscopy Research and Technique, 54, 81–94.PubMedCrossRefGoogle Scholar
  35. Stoll, G., Jander, S., & Myers, R. R. (2002). Degeneration and regeneration of the peripheral nervous system: From Augustus Waller’s observations to neuroinflammation. Journal of the Peripheral Nervous System, 7, 13–27.PubMedCrossRefGoogle Scholar
  36. Yang, R. Y., Rabinovich, G. A., & Liu, F. T. (2008). Galectins: Structure, function and therapeutic potential. Expert Reviews in Molecular Medicine, 10, e17.PubMedCrossRefGoogle Scholar
  37. Yiu, G., & He, Z. (2006). Glial inhibition of CNS axon regeneration. Nature Reviews Neuroscience, 7, 617–627.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press 2009

Authors and Affiliations

  1. 1.Department of Medical Neurobiology, IMRICHebrew University-Hadassah Medical School and the Eric Roland Center for Neurodegenerative DiseasesJerusalemIsrael

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