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Ultrastructural localization of immunoglobulin G and complement C9 in the brain stem and spinal cord following peripheral nerve injury: an immunoelectron microscopic study

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Journal of Neurocytology

Abstract

Summary

The ultrastructural localization of immunoreactivity for immunoglobulin G (IgG), F(ab′)2 and complement C9 was examined with preembedding immunoelectron microscopy in the hypoglossal nucleus and gracile nucleus as well as in the L4 spinal cord dorsal horn 1 week following hypoglossal or sciatic nerve transection, respectively. Only a few scattered immunoreactive profiles were observed on the unoperated side. On the operated side, IgG and F(ab′)2 immunoreactivity was present in the membranes of all reactive microglial cells observed. In addition, the cell membrane of some hypoglossal motoneurons showed IgG immunoreactivity. Complement C9 immunoreactivity was present in the cytoplasm of all reactive microglial cells examined. In addition, there was diffuse C9 immunoreactivity in motoneuron perikarya ipsilateral to nerve injury as well as in cell membranes in the neuropil, some of which could be identified as neuronal. Our interpretation of these findings is (1) that peripheral nerve injury results in binding of IgG to reactive microglia, as well as to some axotomized neurons, and (2) that C9 is synthesized by reactive microglia in response to axon injury and is also associated with axotomized motoneurons. These findings suggest that IgG and complement C9 are involved in microglia-neuron interactions after peripheral nerve injury.

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References

  • Aldskogius, H. & Kozlova, E.N. (1998) Central neuron-glial and glial-glial interactions following axon injury. Progress in Neurobiology 54, 1-26.

    Google Scholar 

  • Aldskogius, H. & Svensson, M. (1993) Neuronal and glial cell responses to axon injury. In: Advances in Structural Biology, Vol. 2 (edited byMalhotra, S.K.), pp. 191-223. Greenwich, CT: JAI Press

    Google Scholar 

  • Bellander, B.M., von Holst, H., Fredman, P. & Svensson, M. (1996) Activation of the complement cascade and increase of clusterin in the brain following a cortical contusion in the adult rat. Journal of Neurosurgery 85, 468-75.

    Google Scholar 

  • Blinzinger, K. & Kreutzberg, G. (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Zeitschrift für Zellforschung und Mikroskopische Anatomie 85, 145-57.

    Google Scholar 

  • Broadwell, R.D. & Sofroniew, M.V. (1993) Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system. Experimental Neurology 120, 245-63.

    Google Scholar 

  • Brown, E.J. (1991) Complement receptors and phagocytosis. Current Opinion in Immunology 3, 76-82.

    Google Scholar 

  • BrÑck, W. & Friede, R.L. (1991) The role of complement in myelin phagocytosis during PNS wallerian degeneration. Journal of the Neurological Sciences 103, 182-7.

    Google Scholar 

  • Dankert, J.R. & Esser, A.F. (1987) Bacterial killing by complement. C9-mediated killing in the absence of C5b-8. Biochemical Journal 244, 393-9.

    Google Scholar 

  • Fabian, R.H. (1988) Uptake of plasma IgG by CNS motoneurons: comparison of antineuronal and normal IgG. Neurology 38, 1775-80.

    Google Scholar 

  • Fabian, R.H. & Petroff, G. (1987) Intraneuronal IgG in the central nervous system: uptake by retrograde axonal transport. Neurology 37, 1780-4.

    Google Scholar 

  • Frank, M.M. & Fries, L.F. (1991) The role of complement in inflammation and phagocytosis. Immunology Today 12, 322-6.

    Google Scholar 

  • Gasque, P., Chan, P., Fontaine, M., Ischenko, A., Lamacz, M., Gotze, O. & Morgan, B.P. (1995a) Identification and characterization of the complement C5a anaphylatoxin receptor on human astrocytes. Journal of Immunology 155, 4882-9.

    Google Scholar 

  • Gasque, P., Fontaine, M. & Morgan, B.P. (1995b) Complement expression in human brain. Biosynthesis of terminal pathway components and regulators in human glial cells and cell lines. Journal of Immunology 154, 4726-33.

    Google Scholar 

  • Gasque, P., Singhrao, S.K., Neal, J.W., Wang, P., Sayah, S., Fontaine, M. & Morgan, B.P. (1998) The receptor for complement anaphylatoxin C3a is expressed by myeloid cells and nonmyeloid cells in inflamed human central nervous system-analysis in multiple sclerosis and bacterial meningitis. Journal of Immunology 160, 3543-54.

    Google Scholar 

  • Hol, E.M., Gispen, W.H. & BÄr, P.R. (1995) ACTH-related peptides: receptors and signal transduction systems involved in their neurotrophic and neuroprotective action. Peptides 16, 979-93.

    Google Scholar 

  • Hurley, S.D. & Streit, W.J. (1996) Microglia and the mononuclear phagocyte system. In: Topical Issues in Microglial Research (edited by Ling, E.A., Tan, C.K. & Tan, C.B.C.), pp. 1-19, Singapore Neuroscience Association

  • Itagaki, S., Akiyama, H., Saito, H. & McGeer, P.L. (1994) Ultrastructural localization of complement membrane attack complex (MAC)-like immunoreactivity in brains of patients with Alzheimer′s disease. Brain Research 645, 78-84.

    Google Scholar 

  • Johnson, S., Young Chan, C.S., Laping, N.J. & Finch, C.E. (1996) Perforant path transection induces complement C9 deposition in hippocampus. Experimental Neurology 138, 198-205.

    Google Scholar 

  • Liszewski, M.K. & Atkinson, J.P. (1993) The complement system. In: Fundamental Immunology (edited by Paul, W.E.), pp. 917-39. New York: Raven Press

    Google Scholar 

  • Liu, L., TÖrnqvist, E., Mattsson, P., Eriksson, N.P., Persson, J.K., Morgan, B.P., Aldskogius, H. & Svensson, M. (1995) Complement and clusterin in the spinal cord dorsal horn and gracile nucleus following sciatic nerve injury in the adult rat. Neuroscience 68, 167-79.

    Google Scholar 

  • Mackay, S.L. & Dankert, J.R. (1990) Bacterial killing and inhibition of inner membrane activity by C5b-9 complexes as a function of the sequential addition of C9 to C5b-8 sites. Journal of Immunology 145, 3367-71.

    Google Scholar 

  • Mattsson, P., Morgan, B.P. & Svensson, M. (1998) Complement activation and CD59 expression in the motor facial nucleus following intracranial transection of the facial nerve in the adult rat. Journal of Neuroimmunology, in press.

  • McGeer, E.G. & McGeer, P.L. (1997) The role of the immune system in neurodegenerative disorders. Movement Disorders 12, 855-88.

    Google Scholar 

  • McPhaden, A.R. & Whaley, K. (1993) Complement biosynthesis by mononuclear phagocytes. Immunology Research 12, 213-32.

    Google Scholar 

  • Moos, T., Stagaard, M. & Mollgard, K. (1991) Immunocytochemical evidence for retrograde axonal transport of exogenous albumin in adult rat brain stem motor neurons. Neuroscience Letters 127, 1-4.

    Google Scholar 

  • Morgan, B.P. (1992) Effects of the membrane attack complex of complement on nucleated cells. Current Topics in Microbiology and Immunology 178, 115-40.

    Google Scholar 

  • Morgan, B.P., Gasque, P., Singhrao, S.K. & Piddlesden, S.J. (1997) Role of complement in inflammation and injury in the nervous system. Experimental and Clinical Immunogenetics 14, 19-23.

    Google Scholar 

  • Mitin, Y.V., Navolotskaya, E.V., Vasilenko, R.N., Abramov, V.M. & Zav′yalov, V.P. (1993) Synthesis and properties of the peptide corresponding to the ACTH-like sequence of human immunoglobulin G1. International Journal of Peptide & Protein Research 41, 517-21.

    Google Scholar 

  • Perry, V.H., Bell, M.D., Brown, H.C. & Matyszak, M.K. (1995) Inflammation in the nervous system. Current Opinion in Neurobiology 5, 636-41.

    Google Scholar 

  • Piddlesden, S.J., Storch, M.K., Hibbs, M., Freeman, A.M., Lassmann, H. & Morgan, B.P. (1994) Soluble recombinant complement receptor 1 inhibits inflammation and demyelination in antibody-mediated demyelinating experimental allergic encephalomyelitis. Journal of Immunology 152, 5477-84.

    Google Scholar 

  • Sayah, S., PTE, C., Gasque, P., Chan, P., Ischenko, A., Vaudry, H. & Fontaine, M. (1997) Characterization of rat C5a anaphylatoxin receptor (C5aR): cloning of rat C5aR cDNAand study of C5aR expression by rat astrocytes. Molecular Brain Research 48, 215-22.

    Google Scholar 

  • Strand, F.L., Williams, K.A., Alver, S.E., Antonawich, F.J., Lee, T.S, Lee, S.J., Kume, J. & Zuccarelli, L.A. (1994) Melanocortins as factors in somatic neuromuscular growth and regrowth. Pharmacology and Therapeutics 62, 1-27.

    Google Scholar 

  • Svensson, M. & Aldskogius, H. (1992) Evidence for activation of the complement cascade in the hypoglossal nucleus following peripheral nerve injury. Journal of Neuroimmunology 40, 99-109.

    Google Scholar 

  • Svensson, M., Liu, L., Mattsson, P., Morgan, B.P. & Aldskogius, H. (1995) Evidence for activation of the terminal pathway of complement and upregulation of sulfated glycoprotein (SGP)-2 in the hypoglossal nucleus following peripheral nerve injury. Molecular and Chemical Neuropathology 24, 53-68.

    Google Scholar 

  • Terai, K., Walker, D.G., McGeer, E.G. & McGeer, P.L. (1997) Neurons express proteins of the classical complement pathway in Alzheimer disease. Brain Research 769, 385-90.

    Google Scholar 

  • Tyor, W.R., Wesselingh, S., Levine, B. & Griffin, D.E. (1992) Long term intraparenchymal Ig secretion after acute viral encephalitis in mice. Journal of Immunology 149, 4016-20.

    Google Scholar 

  • Walport, M. (1993) Complement. Chapter 12. In: Immunology (edited by Roitt, I.), Chapter 12. St Louis, London: Mosby.

    Google Scholar 

  • Wood, A., Wing, M.G., Benham, C.D. & Compston, D.A. (1993) Specific induction of intracellular calcium oscillations by complement membrane attack on oligodendroglia. Journal of Neuroscience 13, 3319-32.

    Google Scholar 

  • Yao, J., Harvath, L., Gilbert, D.L. & Colton, C.A. (1990) Chemotaxis by a CNS macrophage, the microglia. Journal of Neuroscience Research 27, 36-42.

    Google Scholar 

  • Young, J.D. & Young, T.M. (1990) Channel fluctuations induced by membrane attack complex C5b-9. Molecular Immunology 27, 1001-7.

    Google Scholar 

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Liu, L., Aldskogius, H. & Svensson, M. Ultrastructural localization of immunoglobulin G and complement C9 in the brain stem and spinal cord following peripheral nerve injury: an immunoelectron microscopic study. J Neurocytol 27, 737–748 (1998). https://doi.org/10.1023/A:1006950917973

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