Skip to main content

Advertisement

Log in

Involvement of Fc Receptors in Disorders of the Central Nervous System

  • Review Paper
  • Published:
NeuroMolecular Medicine Aims and scope Submit manuscript

Abstract

Immunoglobulins are proteins with a highly variable antigen-binding domain and a constant region (Fc domain) that binds to a cell surface receptor (FcR). Activation of FcRs in immune cells (lymphocytes, macrophages, and mast cells) triggers effector responses including cytokine production, phagocytosis, and degranulation. In addition to their roles in normal responses to infection or tissue injury, and in immune-related diseases, FcRs are increasingly recognized for their involvement in neurological disorders. One or more FcRs are expressed in microglia, astrocytes, oligodendrocytes, and neurons. Aberrant activation of FcRs in such neural cells may contribute to the pathogenesis of major neurodegenerative conditions including Alzheimer’s disease, Parkinson’s disease, ischemic stroke, and multiple sclerosis. On the other hand, FcRs may play beneficial roles in counteracting pathological processes; for e.g., FcRs may facilitate removal of amyloid peptides from the brain and so protect against Alzheimer’s disease. Knowledge of the functions of FcRs in the nervous system in health and disease is leading to novel preventative and therapeutic strategies for stroke, Alzheimer’s disease, and other neurological disorders.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Abramson, J., & Pecht, I. (2007). Regulation of the mast cell response to the type 1 Fc epsilon receptor. Immunological Reviews, 217, 231–254.

    Article  CAS  PubMed  Google Scholar 

  • Akilesh, S., et al. (2008). Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proceedings of the National Academy of Sciences of the United States of America, 105, 967–972.

    Article  CAS  PubMed  Google Scholar 

  • Akiyama, H., et al. (2000). Cell mediators of inflammation in the Alzheimer disease brain. Alzheimer Disease and Associated Disorders, 14, S47–S53.

    Article  CAS  PubMed  Google Scholar 

  • Alliot, F., et al. (1999). Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Research. Developmental Brain Research, 117, 145–152.

    Article  CAS  PubMed  Google Scholar 

  • Amir-Moazami, O., et al. (2008). Phospholipid scramblase 1 modulates a selected set of IgE receptor-mediated mast cell responses through LAT-dependent pathway. The Journal of Biological Chemistry, 283, 25514–25523.

    Article  CAS  PubMed  Google Scholar 

  • Andersson, J., et al. (2005). Intravenous immune globulin affects cytokine production in T lymphocytes and monocytes/macrophages. Clinical And Experimental Medicine, 5, 135–140.

    Article  CAS  Google Scholar 

  • Andoh, T., & Kuraishi, Y. (2004a). Direct action of immunoglobulin G on primary sensory neurons through Fc gamma receptor I. FASEB Journal, 18, 182–184.

    CAS  PubMed  Google Scholar 

  • Andoh, T., & Kuraishi, Y. (2004b). Expression of Fc epsilon receptor I on primary sensory neurons in mice. Neuroreport, 15, 2029–2031.

    Article  CAS  PubMed  Google Scholar 

  • Appel, S., et al. (1992). Nigral damage and dopaminergic hypofunction in mesencephalon-immunized guinea pigs. Annals of Neurology, 32, 494–501.

    Article  CAS  PubMed  Google Scholar 

  • Arumugam, T. V., et al. (2005). Stroke and T-cells. Neuromolecular Medicine, 7, 229–242.

    Article  CAS  PubMed  Google Scholar 

  • Arumugam, T. V., et al. (2006). Gamma secretase-mediated notch signaling worsens brain damage and functional outcome in ischemic stroke. Nature Medicine, 12, 621–623.

    Article  CAS  PubMed  Google Scholar 

  • Arumugam, T. V., et al. (2007). Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death. Proceedings of the National Academy of Sciences of the United States of America, 104, 14104–14109.

    Article  CAS  PubMed  Google Scholar 

  • Arumugam, T. V., et al. (2009). Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience, 158, 1074–1089.

    Article  CAS  PubMed  Google Scholar 

  • Bacskai, B. J., et al. (2002). Non-Fc-mediated mechanisms are involved in clearance of amyloid-beta in vivo by immunotherapy. Journal of Neuroscience, 22, 7873–7878.

    CAS  PubMed  Google Scholar 

  • Baerenwaldt, A., & Nimmerjahn, F. (2008). Immune regulation: FcgammaRIIB–regulating the balance between protective and autoreactive immune responses. Immunology and Cell Biology, 86, 482–484.

    Article  CAS  PubMed  Google Scholar 

  • Bard, F., et al. (2000). Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature Medicine, 6, 916–919.

    Article  CAS  PubMed  Google Scholar 

  • Bard, F., et al. (2003). Epitope and isotype specificities of antibodies to beta -amyloid peptide for protection against Alzheimer’s disease-like neuropathology. Proceedings of the National Academy of Sciences of the United States of America, 100, 2023–2028.

    Article  CAS  PubMed  Google Scholar 

  • Bayry, J., et al. (2007). Monoclonal antibody and intravenous immunoglobulin therapy for rheumatic diseases: Rationale and mechanisms of action. Nature Clinical Practice Rheumatology, 3, 262–272.

    Article  CAS  PubMed  Google Scholar 

  • Beard, C. M., et al. (1998). Nonsteroidal anti-inflammatory drug use and Alzheimer’s disease: A case–control study in Rochester, Minnesota, 1980 through 1984. Mayo Clinic Proceedings, 73, 951–955.

    Article  CAS  PubMed  Google Scholar 

  • Bernstein, J. J., et al. (1993). Sequestering of immunoglobulins by astrocytes after cortical lesion and homografting of fetal cortex. International Journal of Developmental Neuroscience, 11, 117–124.

    Article  CAS  PubMed  Google Scholar 

  • Bracke, M., et al. (1998). Analysis of signal transduction pathways regulating cytokine-mediated Fc receptor activation on human eosinophils. Journal of Immunology, 161, 6768–6774.

    CAS  Google Scholar 

  • Brauweiler, A. M., & Cambier, J. C. (2003). Fc gamma RIIB activation leads to inhibition of signalling by independently ligated receptors. Biochemical Society Transactions, 31, 281–285.

    Article  CAS  PubMed  Google Scholar 

  • Breckwoldt, M. O., et al. (2008). Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proceedings of the National Academy of Sciences of the United States of America, 105, 18584–18589.

    Article  CAS  PubMed  Google Scholar 

  • Bruhns, P., et al. (2000). Molecular basis of the recruitment of the SH2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 by fcgamma RIIB. The Journal of Biological Chemistry, 275, 37357–37364.

    Article  CAS  PubMed  Google Scholar 

  • Chen, S., et al. (1998). Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins. Archives of Neurology, 55, 1075–1080.

    Article  CAS  PubMed  Google Scholar 

  • Coggeshall, K. M. (2002). Regulation of signal transduction by the Fc gamma receptor family members and their involvement in autoimmunity. Current Directions in Autoimmunity, 5, 1–29.

    Article  CAS  PubMed  Google Scholar 

  • Cote-Vélez, M. J., et al. (1999). Low affinity Fc gamma receptors on murine macrophages: Mitogen-activated protein kinase activation and AP-1 DNA binding activity. Immunology Letters, 67, 251–255.

    Article  PubMed  Google Scholar 

  • Cox, D., & Greenberg, S. (2001). Phagocytic signaling strategies: Fc(gamma)receptor-mediated phagocytosis as a model system. Seminars in Immunology, 13, 339–345.

    Article  CAS  PubMed  Google Scholar 

  • Dahlström, A., et al. (1990). Investigations on auto-antibodies in Alzheimer’s and Parkinson’s diseases, using defined neuronal cultures. Journal of Neural Transmission, 29, 195–206.

    PubMed  Google Scholar 

  • Das, P., et al. (2003). Amyloid-beta immunization effectively reduces amyloid deposition in FcRgamma−/− knock-out mice. Journal of Neuroscience, 23, 8532–8538.

    CAS  PubMed  Google Scholar 

  • Davis, R. S., et al. (2001). Identification of a family of Fc receptor homologs with preferential B cell expression. Proceedings of the National Academy of Sciences of the United States of America, 98, 9772–9777.

    Article  CAS  PubMed  Google Scholar 

  • Davis, R. S., et al. (2002). Fc receptor homologs: Newest members of a remarkably diverse Fc receptor gene family. Immunological Reviews, 190, 123–136.

    Article  CAS  PubMed  Google Scholar 

  • Deane, R., et al. (2005). IgG-assisted age-dependent clearance of Alzheimer’s amyloid beta peptide by the blood–brain barrier neonatal Fc receptor. Journal of Neuroscience, 25, 11495–11503.

    Article  CAS  PubMed  Google Scholar 

  • Deane, R., et al. (2009). Clearance of amyloid-beta peptide across the blood–brain barrier: Implication for therapies in Alzheimer’s disease. CNS & Neurological Disorders Drug Targets, 8, 16–30.

    Article  CAS  Google Scholar 

  • Dessaint, J. P., & Capron, A. (1990). Fc epsilon receptor II-positive macrophages and platelets: Potent effector cells in allergy and defence against helminth parasites. Springer Seminars in Immunopathology, 12, 349–363.

    Article  CAS  PubMed  Google Scholar 

  • Dierks, S. E., et al. (1993). The oligomeric nature of the murine Fc epsilon RII/CD23. Implications for function. Journal of Immunology, 150, 2372–2382.

    CAS  Google Scholar 

  • Ebel, C., et al. (2001). Signal transduction via both human low-affinity IgG Fc receptors, Fc gamma RIIa and Fc gamma RIIIb, depends on the activity of different families of intracellular kinases. Immunobiology, 203, 616–628.

    CAS  PubMed  Google Scholar 

  • Falsig, J., et al. (2008). Molecular basis for detection of invading pathogens in the brain. Journal of Neuroscience Research, 86, 1434–1447.

    Article  CAS  PubMed  Google Scholar 

  • Frangione, B., & Wolfenstein-Todel, C. (1972). Partial duplication in the “hinge” region of IgA 1 myeloma proteins. Proceedings of the National Academy of Sciences of the United States of America, 69, 3673–3676.

    Article  CAS  PubMed  Google Scholar 

  • Galon, J., et al. (1996). Soluble Fcgamma receptor type III (FcgammaRIII, CD16) triggers cell activation through interaction with complement receptors. Journal of Immunology, 157, 1184–1192.

    CAS  Google Scholar 

  • Goldstein, B., et al. (2002). Modeling the early signaling events mediated by FcepsilonRI. Molecular Immunology, 38, 1213–1219.

    Article  CAS  PubMed  Google Scholar 

  • Gould, H. J., & Sutton, B. J. (2008). IgE in allergy and asthma today. Nature Reviews Immunology, 8, 205–217.

    Article  CAS  PubMed  Google Scholar 

  • Grant, J. A., et al. (1997). High-affinity IgE receptor Fc epsilon RI expression in allergic reactions. International Archives of Allergy and Immunology, 113, 376–378.

    Article  CAS  PubMed  Google Scholar 

  • Gu, H., et al. (2001). Essential role for Gab2 in the allergic response. Nature, 412, 186–190.

    Article  CAS  PubMed  Google Scholar 

  • Haberman, F., et al. (2007). Soluble neuroprotective antioxidant uric acid analogs ameliorate ischemic brain injury in mice. Neuromolecular Medicine, 9, 315–323.

    Article  CAS  PubMed  Google Scholar 

  • He, Y., et al. (2002). Role of Fcgamma receptors in nigral cell injury induced by Parkinson disease immunoglobulin injection into mouse substantia nigra. Experimental Neurology, 176, 322–327.

    Article  CAS  PubMed  Google Scholar 

  • Heyman, B. (2000). Regulation of antibody responses via antibodies, complement, and Fc receptors. Annual Review of Immunology, 18, 709–737.

    Article  CAS  PubMed  Google Scholar 

  • Hill, J. M., et al. (1985). Transferrin receptors in rat brain: Neuropeptide-like pattern and relationship to iron distribution. Proceedings of the National Academy of Sciences of the United States of America, 82, 4553–4557.

    Article  CAS  PubMed  Google Scholar 

  • Hirsch, E. C., & Hunot, S. (2009). Neuroinflammation in Parkinson’s disease: A target for neuroprotection? Lancet Neurology, 8, 382–397.

    Article  CAS  PubMed  Google Scholar 

  • Holtzman, D. M., et al. (2002). Abeta immunization and anti-Abeta antibodies: Potential therapies for the prevention and treatment of Alzheimer’s disease. Advanced Drug Delivery Reviews, 54, 1603–1613.

    Article  CAS  PubMed  Google Scholar 

  • Huang, Z. Y., et al. (2003). The effect of phosphatases SHP-1 and SHIP-1 on signaling by the ITIM- and ITAM-containing Fcgamma receptors FcgammaRIIB and FcgammaRIIA. Journal of Leukocyte Biology, 73, 823–829.

    Article  CAS  PubMed  Google Scholar 

  • Hulse, K. E., & Woodfolk, J. A. (2008). Targeting allergen to Fc gammaRI: A strategy to treat allergic disease? Current Opinion in Allergy and Clinical Immunology, 8, 547–552.

    Article  CAS  PubMed  Google Scholar 

  • Hunot, S., et al. (1999). FcepsilonRII/CD23 is expressed in Parkinson’s disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. Journal of Neuroscience, 19, 3440–3447.

    CAS  PubMed  Google Scholar 

  • Ishikawa, M., et al. (2005). CD40/CD40 ligand signaling in mouse cerebral microvasculature after focal ischemia/reperfusion. Circulation, 111, 1690–1696.

    Article  CAS  PubMed  Google Scholar 

  • Ivashkiv, L. B. (2009). Cross-regulation of signaling by ITAM-associated receptors. Nature Immunology, 10, 340–347.

    Article  CAS  PubMed  Google Scholar 

  • Jabril-Cuenod, B., et al. (1996). Sykdependent phosphorylation of Shc: A potential link between FcepsilonRI and the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2. The Journal of Biological Chemistry, 271, 16268–16272.

    Article  CAS  PubMed  Google Scholar 

  • Jakus, Z., et al. (2009). Critical role of phospholipase Cgamma2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis. Journal of Experimental Medicine, 206, 577–593.

    Article  CAS  PubMed  Google Scholar 

  • Jin, C. Y., et al. (2006). Piceatannol attenuates lipopolysaccharide-induced NF-kappaB activation and NF-kappaB-related proinflammatory mediators in BV2 microglia. Pharmacological Research, 54, 461–467.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, S. A., et al. (1995). Phosphorylated immunoreceptor signaling motifs (ITAMs) exhibit unique abilities to bind and activate Lyn and Syk tyrosine kinases. Journal of Immunology, 155, 4596–4603.

    CAS  Google Scholar 

  • Johnson, S., et al. (1996). Perforant path transection induces complement C9 deposition in hippocampus. Experimental Neurology, 138, 198–205.

    Article  CAS  PubMed  Google Scholar 

  • Joshi, T., et al. (2006). Molecular analysis of expression and function of hFcgammaRIIbl and b2 isoforms in myeloid cells. Molecular Immunology, 43, 839–850.

    Article  CAS  PubMed  Google Scholar 

  • Kaur, C., & Ling, E. A. (1999). Increased expression of transferrin receptors and iron in amoeboid microglial cells in postnatal rats following an exposure to hypoxia. Neuroscience Letters, 262, 183–186.

    Article  CAS  PubMed  Google Scholar 

  • Kimata, H. (2007). Specific allergen enhances IgE production via galectin-3 in surface IgE+ B cells. European Journal of Clinical Investigation, 37, 1001–1002.

    Article  CAS  PubMed  Google Scholar 

  • Kitaura, J., et al. (2000). Akt-dependent cytokine production in mast cells. Journal of Experimental Medicine, 192, 729–740.

    Article  CAS  PubMed  Google Scholar 

  • Komine-Kobayashi, M., et al. (2004). Dual role of Fcgamma receptor in transient focal cerebral ischemia in mice. Stroke, 35, 958–963.

    Article  CAS  PubMed  Google Scholar 

  • Kopeć, A., Panaszek, B., & Fal, A. M. (2006). Intracellular signaling pathways in IgE-dependent mast cell activation. Archivum Immunologiae et Therapiae Experimentalis, 54, 393–401.

    Article  PubMed  CAS  Google Scholar 

  • Lakshmi Tamma, S. M., et al. (2001). IgD receptor-mediated signal transduction in T cells. Cellular Immunology, 207, 110–117.

    Article  CAS  PubMed  Google Scholar 

  • Lalancette-Hébert, M., et al. (2007). Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. Journal of Neuroscience, 27, 2596–2605.

    Article  PubMed  CAS  Google Scholar 

  • Lang, M. L., & Kerr, M. A. (2000). Characterization of FcalphaR-triggered Ca(2+) signals: Role in neutrophil NADPH oxidase activation. Biochemical and Biophysical Research Communications, 276, 749–755.

    Article  CAS  PubMed  Google Scholar 

  • Le, W. D., et al. (1995). Experimental autoimmune nigral damage in guinea pigs. Journal of Neuroimmunology, 57, 45–53.

    Article  CAS  PubMed  Google Scholar 

  • Le, W. D., et al. (1999). Effects of cerebrospinal fluid from patients with Parkinson disease on dopaminergic cells. Archives of Neurology, 56, 194–200.

    Article  CAS  PubMed  Google Scholar 

  • Lees, A. J., et al. (2009). Parkinson’s disease. Lancet, 373, 2055–2066.

    Article  CAS  PubMed  Google Scholar 

  • Levites, Y., et al. (2006). Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer’s disease mouse models. FASEB Journal, 20, 2576–2578.

    Article  CAS  PubMed  Google Scholar 

  • Li, Y. N., et al. (2008). Alterations of Fc gamma receptor I and Toll-like receptor 4 mediate the antiinflammatory actions of microglia and astrocytes after adrenaline-induced blood–brain barrier opening in rats. Journal of Neuroscience Research, 86, 3556–3565.

    Article  CAS  PubMed  Google Scholar 

  • Liesz, A., et al. (2009). Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nature Medicine, 15, 192–199.

    Article  CAS  PubMed  Google Scholar 

  • Loughlin, A. J., et al. (1992). Regulation of Fc receptor and major histocompatibility complex antigen expression on isolated rat microglia by tumour necrosis factor, interleukin-1 and lipopolysaccharide: Effects on interferon-gamma induced activation. Immunology, 75, 170–175.

    CAS  PubMed  Google Scholar 

  • Loughlin, A. J., et al. (1993). Modulation of interferon-gamma-induced major histocompatibility complex class II and Fc receptor expression on isolated microglia by transforming growth factor-beta 1, interleukin-4, noradrenaline and glucocorticoids. Immunology, 79, 125–130.

    CAS  PubMed  Google Scholar 

  • Love, S. (1999). Oxidative stress in brain ischemia. Brain Pathology, 9, 119–131.

    Article  CAS  PubMed  Google Scholar 

  • Lyden, T. W., et al. (2001). The Fc receptor for IgG expressed in the villus endothelium of human placenta is Fc gamma RIIb2. Journal of Immunology, 166, 3882–3889.

    CAS  Google Scholar 

  • Ma, Y., et al. (2006). Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. Journal of Cell Biology, 175, 209–215.

    Article  CAS  PubMed  Google Scholar 

  • Malbec, O., et al. (2002). Negative regulation of mast cell proliferation by FcgammaRIIB. Molecular Immunology, 38, 1295–1299.

    Article  CAS  PubMed  Google Scholar 

  • Manetz, T. S., et al. (2001). Vav1 regulates phospholipase cgamma activation and calcium responses in mast cells. Molecular and Cellular Biology, 21, 3763–3774.

    Article  CAS  PubMed  Google Scholar 

  • Mangin, P., et al. (2003). Signaling role for phospholipase C gamma 2 in platelet glycoprotein Ib alpha calcium flux and cytoskeletal reorganization. Involvement of a pathway distinct from FcR gamma chain and Fc gamma RIIA. The Journal of Biological Chemistry, 278, 32880–32891.

    Article  CAS  PubMed  Google Scholar 

  • Mash, D. C., et al. (1990). Characterization and distribution of transferrin receptors in the rat brain. Journal of Neurochemistry, 55, 1972–1979.

    Article  CAS  PubMed  Google Scholar 

  • Mattson, M. P. (2004). Pathways towards and away from Alzheimer’s disease. Nature, 430, 631–639.

    Article  CAS  PubMed  Google Scholar 

  • McGeer, P. L., et al. (2006). Inflammation, anti-inflammatory agents and Alzheimer disease: The last 12 years. Journal of Alzheimer’s Disease, 9, 271–276.

    CAS  PubMed  Google Scholar 

  • McRae-Degueurce, A., et al. (1988). Immunocytochemical investigations on the presence of neuron-specific antibodies in the CSF of Parkinson’s disease cases. Neurochemical Research, 13, 679–684.

    Article  CAS  PubMed  Google Scholar 

  • Mélik-Parsadaniantz, S., & Rostène, W. (2008). Chemokines and neuromodulation. Journal of Neuroimmunology, 198, 62–68.

    Article  PubMed  CAS  Google Scholar 

  • Merrill, J. E., et al. (1980a). A T lymphocyte subpopulation in multiple sclerosis patients bearing Fc receptors for both IgG and IgM1. Journal of Immunology, 124, 2758–2764.

    CAS  Google Scholar 

  • Merrill, J. E., et al. (1980b). Identification of three FcR-positive T cell subsets (T gamma, T mu and T gamma mu) in the cerebrospinal fluid of multiple sclerosis patients. Clinical and Experimental Immunology, 42, 345–354.

    CAS  PubMed  Google Scholar 

  • Mina-Osorio, P., & Ortega, E. (2004). Signal regulators in FcR-mediated activation of leukocytes? Trends in Immunology, 25, 529–535.

    Article  CAS  PubMed  Google Scholar 

  • Minskoff, S. A., et al. (1998). Fc gamma RII-B1 regulates the presentation of B cell receptor-bound antigens. Journal of Immunology, 161, 2079–2083.

    CAS  Google Scholar 

  • Mohamed, H. A., et al. (2002). Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons. Journal of Neuroscience Research, 69, 110–116.

    Article  CAS  PubMed  Google Scholar 

  • Monteiro, R. C., & Van De Winkel, J. G. (2003). IgA Fc receptors. Annual Review of Immunology, 21, 177–204.

    Article  CAS  PubMed  Google Scholar 

  • Moos, T., et al. (1999). Iron-independent neuronal expression of transferrin receptor mRNA in the rat. Brain Research. Developmental Brain Research, 72, 231–234.

    CAS  Google Scholar 

  • Moura, I. C., et al. (2001). Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy. Journal of Experimental Medicine, 194, 417–425.

    Article  CAS  PubMed  Google Scholar 

  • Mukhopadhyay, S., et al. (2001). Bruton’s tyrosine kinase associates with the actin-based cytoskeleton in activated platelets. Journal of Cellular Biochemistry, 81, 659–665.

    Article  CAS  PubMed  Google Scholar 

  • Muraille, E., et al. (2000). The SH2 domain containing inositol 5-phosphatase SHIP2 associates to the immunoreceptor tyrosine-based inhibition motif of Fc gammaRIIB in B cells under negative signaling. Immunology Letters, 72, 7–15.

    Article  CAS  PubMed  Google Scholar 

  • Nakahara, J., & Aiso, S. (2006). Fc receptor-positive cells in remyelinating multiple sclerosis lesions. Journal of Neuropathology and Experimental Neurology, 65, 582–591.

    Article  CAS  PubMed  Google Scholar 

  • Nakahara, J., et al. (2003a). Signaling via immunoglobulin Fc receptors induces oligodendrocyte precursor cell differentiation. Developmental Cell, 4, 841–852.

    Article  CAS  PubMed  Google Scholar 

  • Nakahara, J., et al. (2003b). Expression of Fc receptor for immunoglobulin M in oligodendrocytes and myelin of mouse central nervous system. Neuroscience Letters, 337, 73–76.

    Article  CAS  PubMed  Google Scholar 

  • Nakamura, T., et al. (1993). Characterization of an IgM Fc-binding receptor on human T cells. Journal of Immunology, 151, 6933–6941.

    CAS  Google Scholar 

  • Nakamura, K., et al. (2007). CD3 and immunoglobulin G Fc receptor regulate cerebellar functions. Molecular and Cellular Biology, 27, 5128–5134.

    Article  CAS  PubMed  Google Scholar 

  • Nimmerjahn, F., & Ravetch, J. V. (2008). Fcgamma receptors as regulators of immune responses. Nature Reviews Immunology, 8, 34–47.

    Article  CAS  PubMed  Google Scholar 

  • Nimmerjahn, F., et al. (2005). FcgammaRIV: A novel FcR with distinct IgG subclass specificity. Immunity, 23, 41–51.

    Article  CAS  PubMed  Google Scholar 

  • Ninomiya, N., et al. (1994). Involvement of phosphatidylinositol 3-kinase in Fc gamma receptor signaling. The Journal of Biological Chemistry, 269, 22732–22737.

    CAS  PubMed  Google Scholar 

  • Nishizumi, H., & Yamamoto, Y. (1997). Impaired tyrosine phosphorylation and Ca2+ mobilization, but not degranulation, in Lyn-deficient bone marrow-derived mast cells. Journal of Immunology, 158, 2350–2355.

    CAS  Google Scholar 

  • Nitta, T., et al. (1992). Expression of Fc gamma receptors on astroglial cell lines and their role in the central nervous system. Neurosurgery, 31, 83–87.

    Article  CAS  PubMed  Google Scholar 

  • Ohno, T., et al. (1990). Biochemical nature of an Fc mu receptor on human B-lineage cells. Journal of Experimental Medicine, 172, 1165–1175.

    Article  CAS  PubMed  Google Scholar 

  • Okun, E., et al. (2009). Toll-like receptors in neurodegeneration. Brain Research Reviews, 59, 278–292.

    Article  CAS  PubMed  Google Scholar 

  • Olivera, A., et al. (2006). IgE-dependent activation of sphingosine kinases 1 and 2 and secretion of sphingosine 1-phosphate requires Fyn kinase and contributes to mast cell responses. The Journal of Biological Chemistry, 281, 2515–2525.

    Article  CAS  PubMed  Google Scholar 

  • Orita, T., et al. (1990). Transferrin receptors in injured brain. Acta Neuropathologica, 79, 686–688.

    Article  CAS  PubMed  Google Scholar 

  • Orr, C. F., et al. (2005). A possible role for humoral immunity in the pathogenesis of Parkinson’s disease. Brain, 128, 2665–2674.

    Article  PubMed  Google Scholar 

  • Ouadrhiri, Y., et al. (2002). Effect of IgA on respiratory burst and cytokine release by human alveolar macrophages: Role of ERK1/2 mitogen-activated protein kinases and NF-kappaB. American Journal of Respiratory Cell and Molecular Biology, 26, 315–332.

    CAS  PubMed  Google Scholar 

  • Pardridge, W. M., et al. (1987). Human blood–brain barrier transferrin receptor. Metabolism, 36, 892–895.

    Article  CAS  PubMed  Google Scholar 

  • Park, R. K., et al. (1999). Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling. Blood, 94, 2112–2120.

    CAS  PubMed  Google Scholar 

  • Peress, N. S., et al. (1993). Identification of Fc gamma RI, II and III on normal human brain ramified microglia and on microglia in senile plaques in Alzheimer’s disease. Journal of Neuroimmunology, 48, 71–79.

    Article  CAS  PubMed  Google Scholar 

  • Perry, V. H., et al. (1985). Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience, 15, 313–326.

    Article  CAS  PubMed  Google Scholar 

  • Rakover, I., et al. (2007). Immunotherapy against APP beta-secretase cleavage site improves cognitive function and reduces neuroinflammation in Tg2576 mice without a significant effect on brain abeta levels. Neurodegenerative Diseases, 4, 392–402.

    Article  CAS  PubMed  Google Scholar 

  • Ravetch, J. V., & Bolland, S. (2001). IgG Fc receptors. Annual Review of Immunology, 19, 275–290.

    Article  CAS  PubMed  Google Scholar 

  • Ravetch, J. V., et al. (2001). Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science, 291, 484–486.

    Article  PubMed  Google Scholar 

  • Renedo, M. A., et al. (2001). FcgammaRIIA exogenously expressed in HeLa cells activates the mitogen-activated protein kinase cascade by a mechanism dependent on the endogenous expression of the protein tyrosine kinase Syk. European Journal of Immunology, 31, 1361–1369.

    Article  CAS  PubMed  Google Scholar 

  • Rivera, J., et al. (2008). New insights on mast cell activation via the high affinity receptor for IgE. Advances in Immunology, 98, 85–120.

    Article  CAS  PubMed  Google Scholar 

  • Robbie-Ryan, M., et al. (2003). Cutting edge: Both activating and inhibitory Fc receptors expressed on mast cells regulate experimental allergic encephalomyelitis disease severity. Journal of Immunology, 170, 1630–1634.

    CAS  Google Scholar 

  • Roccatello, D., Quattrocchio, G., Cacace, G., Coppo, R., Sena, L. M., et al. (1993). Removal systems of immunoglobulin A and immunoglobulin A containing complexes in IgA nephropathy and cirrhosis patients. The role of asialoglycoprotein receptors. Laboratory Investigation, 69, 714–723.

    CAS  PubMed  Google Scholar 

  • Roopenian, D. C., & Akilesh, S. (2007). FcRn: The neonatal Fc receptor comes of age. Nature Reviews Immunology, 7, 715–725.

    Article  CAS  PubMed  Google Scholar 

  • Rose, D. M., et al. (1997). Interferon-gamma and transforming growth factor-beta modulate the activation of mitogen-activated protein kinases and tumor necrosis factor-alpha production induced by Fc gamma-receptor stimulation in murine macrophages. Biochemical and Biophysical Research Communications, 238, 256–260.

    Article  CAS  PubMed  Google Scholar 

  • Sada, K., & Yamamura, H. (2003). Protein-tyrosine kinases and adaptor proteins in FcepsilonRI-mediated signaling in mast cells. Current Molecular Medicine, 3, 85–94.

    Article  CAS  PubMed  Google Scholar 

  • Scali, C. (2000). Brain inflammatory reaction in an animal model of neuronal degeneration and its modulation by an anti-inflammatory drug: Implication in Alzheimer’s disease. European Journal of Neuroscience, 12, 1900–1912.

    Article  CAS  PubMed  Google Scholar 

  • Seiwa, C., et al. (2007). Restoration of FcRgamma/Fyn signaling repairs central nervous system demyelination. Journal of Neuroscience Research, 85, 954–966.

    Article  CAS  PubMed  Google Scholar 

  • Shichita, T., et al. (2009). Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury. Nature Medicine, 15, 946–950.

    Article  CAS  PubMed  Google Scholar 

  • Sibéril, S., et al. (2006). Molecular aspects of human FcgammaR interactions with IgG: Functional and therapeutic consequences. Immunology Letters, 106, 111–118.

    Article  PubMed  CAS  Google Scholar 

  • Song, X., et al. (2002). Fcgamma receptor I- and III-mediated macrophage inflammatory protein 1alpha induction in primary human and murine microglia. Infection and Immunity, 70, 5177–5184.

    Article  CAS  PubMed  Google Scholar 

  • Song, X., et al. (2004). Fcgamma receptor signaling in primary human microglia: Differential roles of PI-3K and Ras/ERK MAPK pathways in phagocytosis and chemokine induction. Journal of Leukocyte Biology, 75, 1147–1155.

    Article  CAS  PubMed  Google Scholar 

  • Stevens, B., et al. (2007). The classical complement cascade mediates CNS synapse elimination. Cell, 131, 1164–1178.

    Article  CAS  PubMed  Google Scholar 

  • Stockert, R. J. (1995). The asialoglycoprotein receptor: Relationships between structure, function, and expression. Physiological Reviews, 75, 591–609.

    CAS  PubMed  Google Scholar 

  • Suzuki, T., et al. (2000). Differential involvement of Src family kinases in Fc gamma receptor-mediated phagocytosis. Journal of Immunology, 165, 473–482.

    CAS  Google Scholar 

  • Takai, T., et al. (2003). Fc receptors as potential targets for the treatment of allergy, autoimmune disease and cancer. Current Drug Targets. Immune, Endocrine and Metabolic Disorders, 3, 187–197.

    Article  CAS  PubMed  Google Scholar 

  • Tang, S. C., et al. (2007). Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proceedings of the National Academy of Sciences of the United States of America, 104, 13798–13803.

    Article  CAS  PubMed  Google Scholar 

  • Tang, S. C., et al. (2008). Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal. Experimental Neurology, 213, 114–121.

    Article  CAS  PubMed  Google Scholar 

  • Tarasenko, T., et al. (2007). FcgammaRIIB as a modulator of autoimmune disease susceptibility. Autoimmunity, 40, 409–417.

    Article  CAS  PubMed  Google Scholar 

  • Ting, A. T., et al. (1995). Interaction between lck and syk family tyrosine kinases in Fc gamma receptor-initiated activation of natural killer cells. The Journal of Biological Chemistry, 270, 16415–16421.

    Article  CAS  PubMed  Google Scholar 

  • Tkaczyk, C., et al. (2003). The phospholipase C gamma 1-dependent pathway of Fc epsilon RI-mediated mast cell activation is regulated independently of phosphatidylinositol 3-kinase. The Journal of Biological Chemistry, 278, 48474–48484.

    Article  CAS  PubMed  Google Scholar 

  • Turner, H., & Kinet, J. P. (1999). Signalling through the high-affinity IgE receptor Fc epsilonRI. Nature, 402, B24–B30.

    Article  CAS  PubMed  Google Scholar 

  • Ueyama, T., et al. (2004). Superoxide production at phagosomal cup/phagosome through beta I protein kinase C during Fc gamma R-mediated phagocytosis in microglia. Journal of Immunology, 173, 4582–4589.

    CAS  Google Scholar 

  • Ulvestad, E., et al. (1994). Reactive microglia in multiple sclerosis lesions have an increased expression of receptors for the Fc part of IgG. Journal of the Neurological Sciences, 121, 125–131.

    Article  CAS  PubMed  Google Scholar 

  • Underhill, D. M., & Goodridge, H. S. (2007). The many faces of ITAMs. Trends in Immunology, 28, 66–73.

    Article  CAS  PubMed  Google Scholar 

  • Urich, E., et al. (2006). Autoantibody-mediated demyelination depends on complement activation but not activatory Fc-receptors. Proceedings of the National Academy of Sciences of the United States of America, 103, 18697–18702.

    Article  CAS  PubMed  Google Scholar 

  • Urtz, N., et al. (2004). Early activation of sphingosine kinase in mast cells and recruitment to FcepsilonRI are mediated by its interaction with Lyn kinase. Molecular and Cellular Biology, 24, 8765–8777.

    Article  CAS  PubMed  Google Scholar 

  • Van den Herik-Oudijk, I. E., et al. (1995). Identification of signaling motifs within human Fc gamma RIIa and Fc gamma RIIb isoforms. Blood, 85, 2202–2211.

    PubMed  Google Scholar 

  • Vedeler, C., et al. (1994). Fc receptor for IgG (FcR) on rat microglia. Journal of Neuroimmunology, 49, 19–24.

    Article  CAS  PubMed  Google Scholar 

  • Wang, H. H., et al. (2009). Oxidized low-density lipoprotein induces matrix metalloproteinase-9 expression via a p42/p44 and JNK-dependent AP-1 pathway in brain astrocytes. Glia, 57, 24–38.

    Article  PubMed  Google Scholar 

  • Wilcock, D. M., & Colton, C. A. (2009). Immunotherapy, vascular pathology, and microhemorrhages in transgenic mice. CNS & Neurological Disorders Drug Targets, 8, 50–64.

    Article  CAS  Google Scholar 

  • Wilcock, D. M., Gordon, M. N., Morgan, D., et al. (2003). Intracranially administered anti-Abeta antibodies reduce beta-amyloid deposition by mechanisms both independent of and associated with microglial activation. Journal of Neuroscience, 23, 3745–3751.

    CAS  PubMed  Google Scholar 

  • Williams, M. R., et al. (2000). The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells. Current Biology, 10, 439–448.

    Article  CAS  PubMed  Google Scholar 

  • Wines, B. D., & Hogarth, P. M. (2006). IgA receptors in health and disease. Tissue Antigens, 68, 103–114.

    Article  CAS  PubMed  Google Scholar 

  • Woodroofe, M. N., et al. (1989). Fc receptor density, MHC antigen expression and superoxide production are increased in interferon-gamma-treated microglia isolated from adult rat brain. Immunology, 68, 421–426.

    CAS  PubMed  Google Scholar 

  • Wurzburg, B. A., et al. (2006). Structural changes in the lectin domain of CD23, the low-affinity IgE receptor, upon calcium binding. Structure, 14, 1049–1058.

    Article  CAS  PubMed  Google Scholar 

  • Yenari, M. A., et al. (2006). Microglia potentiate damage to blood–brain barrier constituents: Improvement by minocycline in vivo and in vitro. Stroke, 37, 1087–1093.

    Article  PubMed  Google Scholar 

  • Yilmaz, G., et al. (2006). Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation, 113, 2105–2112.

    Article  PubMed  Google Scholar 

  • Yoo, E. M., & Morrison, S. L. (2005). IgA: An immune glycoprotein. Clinical Immunology, 116, 3–10.

    Article  CAS  PubMed  Google Scholar 

  • Yu, M., et al. (2006). Scaffolding adapter Grb2-associated binder 2 requires Syk to transmit signals from FcepsilonRI. Journal of Immunology, 176, 2421–2429.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thiruma V. Arumugam.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Okun, E., Mattson, M.P. & Arumugam, T.V. Involvement of Fc Receptors in Disorders of the Central Nervous System. Neuromol Med 12, 164–178 (2010). https://doi.org/10.1007/s12017-009-8099-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12017-009-8099-5

Keywords

Navigation