Abstract
Intercellular adhesion molecule 1 (ICAM-1, CD54) is a widely expressed glycoprotein, which plays an important role in leukocyte extravasation and in the interaction of lymphocytes with antigen-presenting cells. In the current study we examined the regulation of ICAM-1 in the mouse facial motor nucleus after facial nerve transection, using immunohistochemistry, confocal laser microscopy and electron microscopy. In the normal facial nucleus ICAM-1 immunoreactivity was restricted to vascular endothelium. Transection of the facial nerve led to a strong and selective upregulation of ICAM-1 on activated microglia. Quantitation of microglial ICAM-1 immunoreactivity revealed a biphasic increase. The first peak 1–2 days post operation paralleling the early stage of microglial activation was followed by a decline at 4–7 days. The second induction of ICAM-1 occured at day 14 accompanying the period of neuronal cell death and microglial phagocytosis of neuronal debris. Immunoelectron microscopy showed strong ICAM-1 reactivity on the cell membrane of activated microglia at day 2. During the second peak (day 14), ICAM-1 was also observed on lymphocytes adhering to phagocytotic microglia forming aggregates around neuronal debris. No immunolabelling was observed on neurons, astrocytes or oligodendroglia. These data suggest the involvement of ICAM-1 in the adhesion of activated microglia, in their phagocytosis of neuronal debris, and also in the interaction with infiltrating lymphocytes following this injury.
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Akiyama, H., Kawamata, T., Yamada, T., Tooyama, I., Ishii, T. & Mcgeer, P. L. (1993) Expression of intercellular adhesion molecule (ICAM)-1 by a subset of astrocytes in Alzheimer disease and some other degenerative neurological disorders. Acta Neuropathologica 85, 628- 34.
Akiyama, H., Tooyama, I., Kondo, H., Ikeda, K., Kimura, H., Mcgeer, E. G. & Mcgeer, P. L. (1994) Early response of brain resident microglia to kainic acid-induced hippocampal lesions. Brain Research 635, 257- 68.
Akiyama, H. & Mcgeer, P. L. (1990) Brain microglia constitutively express beta-2 integrins. Journal of Neuroimmunology 30, 81- 93.
Aloisi, F., Borsellino, G., Samoggia, P., Testa, U., Chelucci, C., Russo, G., Peschle, C. & Levi, G. (1992) Astrocyte cultures from human embryonic brain: characterization and modulation of surface molecules by inflammatory cytokines. Journal of Neuroscience Research 32, 494- 506.
Archelos, J. J., Jung, S., MÄurer, M., Schmied, M., Lassmann, H., Tamatani, T., Miyasaka, M., Toyka, K. V. & Hartung, H. P. (1993) Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM-1. Annals of Neurology 34, 145- 54.
Balasingam, V., Tejada-Berges, T., Wright, E., Bouckova, R. & Yong, V. W. (1994) Reactive astrogliosis in the neonatal mouse brain and its modulation by cytokines. Journal of Neuroscience 14, 846- 56.
Ballantyne, C. M., O'brien, W. E. & Beaudet, A. L. (1989) Nucleotide sequence of the cDNA for murine intercellular adhesion molecule-1 (ICAM-1). Nucleic Acids Research 17, 5853.
Bell, M. D. & Perry, V. H. (1995) Adhesion molecule expression on murine cerebral endothelium following the injection of a proinflammagen or during acute neuronal degeneration. Journal of Neurocytolology 24, 695- 710.
Birdsall, H. H. (1991) Induction of ICAM-1 on human neural cells and mechanisms of neutrophil-mediated injury. American Journal of Pathology 139, 1341- 50.
Blinzinger, K. & Kreutzberg, G. W. (1968) Displacement of synaptic terminals from regenerating motorneurons by microglial cells. Proceedings of the National Academy of Science, (USA) 68, 240- 3.
Bo, L., Peterson, J. W., Mork, S., Hoffman, P. A., Gallatin, W. M., Ransohoff, R. M. & Trapp, B. D. (1996) Distribution of immunoglobulin superfamily members ICAM-1,-2,-3, and the beta 2 integrin LFA-1 in multiple sclerosis lesions. Journal of Neuropathology and Experimental Neurology 55, 1060- 72.
Breard, J., Reinherz, E. L., Kung, P. C., Goldstein, G. & Schlossman, S. F. (1980) A monoclonal antibody reactive with human peripheral blood monocytes. Journal of Immunology 124, 1943- 8.
Butcher, E. C. (1991) Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67, 1033- 6.
Cammermeyer, J.(1965) Histiocytes juxtavascular mitotic cells and microglia cells during retrograde changes in the facial nucleus of rabbits of varying age. Ergebnisse der Anatomie und Entwicklungsgeschichte 38, 195- 229.
Cannella, B., Cross, A. H. & Raine, C. S. (1990) Upregulation and coexpression of adhesion molecules correlate with relapsing autoimmune demyelination in the central nervous system. Journal of Experimental Medicine 172, 1521- 4.
Cannella, B. & Raine, C. S. (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions. Annals of Neurology 37, 424- 35.
CarpÉn, O., Pallai, P., Staunton, D. E. & Springer, T. A. (1992) Association of intercellular adhesion molecule-1 (ICAM-1) with actin-containing cytoskeleton and alpha-actinin. Journal of Cell Biology 118, 1223- 34.
Chiang, C.S., Stalder, A., Samimi, A. & Campbell, I. L. (1994) Reactive gliosis as a consequence of interleukin-6 expression in the brain: studies in transgenic mice. Developmental Neuroscience 16, 212- 21.
Deckert-SchlÜter, M., SchlÜter, D., Hof, H., Wiestler, O. D. & Lassmann, H. (1994) Differential expression of ICAM-1, VCAM-1 and their ligands LFA-1, Mac-1, CD43, VLA-4, and MHC class II antigens in murine Toxoplasma encephalitis: a light microscopic and ultrastructural immunohistochemical study. Journal of Neuropathology and Experimental Neurology 53, 457- 68.
Diamond, M.S., Garcia-Aguilar, J., Bickford, J. K., Corbi, A. L. & Springer, T. A. (1993) The I domain is a major recognition site on the leukocyte integrin Mac-1 (CD11b/CD18) for four distinct adhesion ligands. Journal of Cell Biology 120, 1031- 43.
Dougherty, G., Murdoch, S. & Hogg, N. (1988) The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of an immunresponse. European Journal of Immunology 18, 35- 9.
Durieu-Trautmann, O., Chaverot, N., Cazaubon, S., Strosberg, A. D. & Couraud, P. O. (1994) Intercellular adhesionmolecule 1 activation induces tyrosine phosphorylation of the cytoskeleton-associated protein cortactin in brain microvessel endothelial cells. Journal of Biological Chemistry 269, 12536- 40.
Dustin, M. L., Rothlein, R., Bhan, A. K., Dinarello, C. A. & Springer, T. A. (1986) Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). Journal of Immunology 137, 245- 54.
Fabry, Z., Waldschmidt, M. M., Hendrickson, D., Keiner, J., Love-Homan, L., Takei, F. & Hart, M. N. (1992) Adhesion molecules on murine brain microvascular endothelial cells: expression and regulation of ICAM-1 and Lgp 55. Journal of Neuroimmunology 36, 1- 11.
Fattori, E., Lazzaro, D., Musiani, P., Modesti, A., Alonzi, T. & Ciliberto, G. (1995) IL-6 expression in neurons of transgenic mice causes reactive astrocytosis and increase in ramified microglial cells but no neuronal damage. European Journal of Neuroscience 7, 2441- 9.
Fishman, P.S. & Savitt, J. M. (1989) Selective localization by neuroglia of immunoglobulin G in normal mice. Journal of Neuropathology and Experimental Neurology 48, 212- 20.
Fukuda, M. & Carlsson, S. R. (1986) Leukosialin, a major sialoglycoprotein on human leukocytes as differentiation antigens. Medical Biology 64, 335- 43.
Frohman, E. M., Frohman, T. C., Dustin, M. L., Vayuvegula, B., Choi, B., Gupta, A., van den Noort, S. & Gupta, S. (1989) The induction of intercellular adhesion molecule 1 (ICAM-1) expression on human fetal astrocytes by interferon-gamma, tumor necrosis factor alpha, lymphotoxin, and interleukin-1: relevance to intracerebral antigen presentation. Journal of Neuroimmunology 23, 117- 24.
Graeber, M. B., Streit, W. J. & Kreutzberg, G. W. (1988a) Axotomy of the rat facial nerve leads to increased CR3 complement receptor expression by activated microglial cells. Journal of Neuroscience Research 21, 18- 24.
Graeber, M. B., Tetzlaff, W., Streit, W. J. & Kreutzberg, G. W. (1988b) Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy. Neuroscience Letters 85, 317- 21.
Graeber, M. B. & Kreutzberg, G. W. (1988) Delayed astrocyte reaction following facial nerve axotomy.Journal of Neurocytology 17, 209- 20.
Greenwood, J., Wang, Y. & Calder, V. L. (1995) Lymphocyte adhesion and transendothelial migration in the central nervous system: the role of LFA-1, ICAM-1, VLA-4 and VCAM-1. Immunology 86, 408- 15.
Haskard, D., Cavender, D., Beatty, P., Springer, T. A. & Ziff, M. (1986) T lymphocyte adhesion to endothelial cells: mechanisms demonstrated by anti-LFA-1 monoclonal antibodies. Journal of Immunology 137, 2901- 6.
Horley, K.J., Carpenito, C., Baker, B. & Takei, F. (1989) Molecular cloning of murine intercellular adhesion molecule (ICAM-1). EMBO Journal 8, 2889- 96.
Irani, D.N. & Griffin, D. E. (1996) Regulation of lymphocyte homing into the brain during viral encephalitis at various stages of infection. Journal of Immunology 156, 3850- 7.
Kato, H., Kogure, K., Liu, X. H., Araki, T. & Itoyama, Y. (1996) Progressive expression of immunomolecules on activated microglia and invading leukocytes following focal cerebral ischemia in the rat. Brain Research 734, 203- 12.
Kelly, K. J., Williams, W. W., Jr., Colvin, R. B., Meehan, S. M., Springer, T. A., Gutierrez-Ramos, J. C. & Bonventre, J. V. (1996) Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury. Journal of Clinical Investigation 97, 1056- 63.
Kiefer, R., Lindholm, D. & Kreutzberg, G. W. (1993) Interleukin-6 and transforming growth factorbeta 1 mRNAs are induced in rat facial nucleus following motoneuron axotomy. European Journal of Neuroscience 5, 775- 81.
Klein, M. A., Möller, J. C., Jones, L. L., BlÜthmann, H., Kreutzberg, G. W. & Raivich, G. (1997) Impaired neuroglial activation in interleukin-6 deficient mice. Glia 19, 227- 33.
Konno, H., Yamamoto, T., Suzuki, H., Yamamoto, H., Iwasaki, Y., Ohara, Y., Terunuma, H. & harata, N. (1990) Targeting of adoptively transferred experimental allergic encephalitis lesion at the sites of wallerian degeneration. Acta Neuropathologica 80, 521- 6.
Kreutzberg, G. W. (1966) Autoradiographische Untersuchung über die Beteiligung von Gliazellan an der axonalen Reaktion im Facialiskern de Ratte. Acta Neuropathologica (Berl) 7, 149- 61.
Kreutzberg, G. W. & Barron, K. D. (1978) 5′-Nucleotidase of microglial cells in the facial nucleus during axonal reaction. Journal of Neurocytology 7, 601- 10.
Kreutzberg, G. W. (1986) The Facial Nerve. In: Neurobiology of regeneration and degeneration (edited by MAY, M.), pp. 75- 84. New York: Thieme.
Kreutzberg, G. W. (1996) Microglia: a sensor for pathological events in the CNS. Trends in Neurosciences 19, 312- 8.
Kurzinger, K., Reynolds, T., Germain, R. N., Davignon, D., Martz, E. & Springer, T. A. (1981) A novel lymphocyte function-associated antigen (LFA-1): cellular distribution, quantitative expression, and structure. Journal of Immunology 127, 596- 602.
Lindsberg, P. J., Carpen, O., Paetau, A., Karjalainen-Lindsberg, M. L. & Kaste, M. (1996) Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke. Circulation 94, 939- 45.
Lukacs, N. W., Strieter, R. M., Elner, V. M., Evanoff, H. L., Burdick, M. & Kunkel, S. L. (1994) Intercellular adhesion molecule-1 mediates the expression of monocyte-derived MIP-1 alpha during monocyte-endothelial cell interactions. Blood 83, 1174- 8.
Mander, T. H. & Morris, J. F. (1997) Immunophenotypic evidence for distinct populations of microglia in the rat hypothalamo-neurohypophysical system. Cell and Tissue Research 280, 665- 73.
Matsui, M. & Kuroda, Y. (1997) Aberrant immunity in the central nervous system in relation to disease progression in HAM/TSP. Clinical Immunology and Immunopathology 82, 203- 6.
Matsumoto, Y., Hara, N., Tanaka, R. & Fujiwara, M. (1986) Immunohistochemical analysis of the rat central nervous system during experimental allergic encephalomyelitis, with special reference to Iapositive cells with dendritic morphology. Journal of Immunology 136, 3668- 76.
Matsuo, A., Walker, D. G., Terai, K. & Mcgeer, P. L. (1996) Expression of cd43 in human microglia and its down-regulation in alzheimers-disease. Journal of Neuroimmunology 71, 81- 6.
Mitrovic, B., Martin, F. C., Charles, A. C., Ignarro, L. J., Anton, P. A., Shanahan, F. & Merrill, J. E. (1994) Neurotransmitters and cytokines in CNS pathology Progress in Brain Research 103, 319- 30.
Moffett, C. W., Paden, C. M. (1994) Microglia in the rat neurohypophysis increase expression of class I major histocompatibility antigens following central nervous system injury. Journal of Neuroimmunology 50, 139- 51.
Möller, J. C., Klein, M. A., Haas, S., Jones, L. L., Kreutzberg, G. W. & Raivich, G. (1996) Regulation of thrombospondin in the regenerating mouse facial motor nucleus. Glia 17, 121- 32.
Moneta, M. E., Gehrmann, J., Töpper, R., Banati, R. B. & Kreutzberg, G. W. (1993) Cell adhesion molecule expression in the regenerating rat facial nucleus. Journal of Neuroimmunology 45, 203- 6.
Morganti-Kossmann, M. C., Kossmann, T. & Wahl, S. M. (1992) Cytokines and neuropathology. Trends in Pharmacological Sciences 13, 286- 91.
Möst, J., Schwaeble, W. & Dierich, M. P. (1992) Expression of intercellular adhesion molecule-1 (ICAM-1) on human monocytes. Immunobiology 185, 327- 36.
O'neill, J. K., Butter, C., Baker, D., Gschmeissner, S. E., Kraal, G., Butcher, E. C. & Turk, J. L. (1991) Expression of vascular addressins and ICAM-1 by endothelial cells in the spinal cord during chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse. Immunology 72, 520- 5.
Perry, V. H., Crocker, P. R. & Gordon, S. (1992) The blood-brain barrier regulates the expression of a macrophage sialic acid-binding receptor on microglia. Journal of Cell Science 101, 201- 7.
Perry, V. H., Gordon, S. (1987) Modulation of CD4 antigen on macrophages and microglia in rat brain. Journal of Experimental Medicine 166, 1138- 43.
Pitzalis, C., Sharrack, B., Gray, I. A., Lee, A. & Hughes, R. A. (1997) Comparison of the effects of oral versus intravenous methylprednisolone regimens on peripheral blood T lymphocyte adhesion molecule expression, T cell subsets distribution and TNF alpha concentrations in multiple sclerosis. Journal of Neuroimmunology 74, 62- 8.
Raivich, G., Moreno-Flores, M. T., Möller, J. C. & Kreutzberg, G. W. (1994) Inhibition of posttraumatic microglial proliferation in a genetic model of macrophage colony-stimulating factor deficiency in the mouse. European Journal of Neuroscience 6, 1615- 8.
Raivich, G., BlÜthmann, H. & Kreutzberg, G. W. (1996) Signaling molecules and neuroglial activation in the injured central nervous system. Keio Journal of Medicine 45, 239- 47.
Remold-O'donnell, E., Zimmerman, C., Kenney, D. & Rosen, F. S. (1987) Expression on blood cells of sialophorin, the surface glycoprotein that is defective in Wiskott-Aldrich syndrome. Blood 70, 104- 9.
Richards, I. M., Kolbasa, K. P., Winterrowd, G. E., Hatfield, C. A., Vonderfecht, S. L., Fidler, S. F., Griffin, R. L., Brashler, J. R., Krzesicki, R. F., Lane, C. L., Anderson, D. C., Sly, L. M., Staite, N. D. & Chin, J. E. (1996) Role of intercellular adhesion molecule-1 in antigen-induced lung inflammation in brown Norway rats. American Journal of Physiology 271, 267- 76.
Rosenstein,Y., Park, J. K., Hahn, W. C., Rosen, F. S., Bierer, B. E. & Burakoff, S. J. (1991) CD43, a molecule defective in Wiskott-Aldrich syndrome, binds ICAM-1. Nature 354, 233- 5.
RÖssler, K., Neuchrist, C., Kitz, K., Scheiner, O., Kraft, D. & Lassmann, H. (1992) Expression of leucocyte adhesion molecules at the human blood- brain barrier (BBB). Journal of Neuroscience Research 31, 365–74.
Sanchez-Madrid, F., Nagy, J. A., Robbins, E., Simon, P. & Springer, T. A. (1983) A human leukocyte differentiation antigen family with distinct alphasubunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150, 95 molecule. Journal of Experimental Medicine 158, 1785- 803.
Schwarting, R., Stein, H. & Wang, C. Y. (1985) The monoclonal antibodies alpha S-HCL 1 (alpha Leu-14) and alpha S-HCL 3 (alpha Leu-M5) allow the diagnosis of hairy cell leukemia. Blood 65, 974- 83.
Shimizu, Y., Van Sventer, G., Horgan, K. & Shaw, S. (1990) Roles of adhesion molecules in T cell recognition: fundamental similarities between four integrins on resting human T cells (LFA-1, VLA-4, VLA-4, VLA-6) in expression, binding and co-stimulation. Immunology Review 114, 109- 43.
Shrikant, P., Chung, I. Y., Ballestas, M. E. & Benveniste, E. N. (1994) Regulation of intercellular adhesion molecule-1 gene expression by tumor necrosis factor-alpha, interleukin-1 beta, and interferongamma in astrocytes. Journal of Neuroimmunology 51, 209- 20.
Shrikant, P., Weber, E., Jilling, T. & Benveniste, E. N. (1995) Intercellular adhesion molecule-1 gene expression by glial cells. Differential mechanisms of inhibition by IL-10 and IL-6. Journal of Immunology 155, 1489- 501.
Shrikant, P., Lee, S. J., Kalvakolanu, I., Ransohoff, R. M. & Benveniste, E. N. (1996) Stimulus-specific inhibition of intracellular adhesion molecule-1 gene expression by TGF-beta. Journal of Immunology 157, 892- 900.
Simmons, D., Makgoba, M. W. & Seed, B. (1998) ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature 331, 624- 7.
SjÖstrand, J. (1996) Studies on glial cells in the hypoglossal nucleus of the rabbit during nerve regeneration. Acta Physiologica Scandinavica 67 (Suppl. 270), 1- 17.
Springer, T. A., Teplow, D. B. & Dreyer, W. J. (1985) Sequence homology of the LFA-1 and Mac-1 leukocyte adhesion glycoproteins and unexpected relation to leukocyte interferon. Nature 314, 540- 2.
Springer, T.A. (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76, 301- 14.
Staunton, D. E., Marlin S. D., Stratowa C., Dustin M. L. & Springer T. A. (1998) Primary structure of ICAM-1 demonstrates interaction between members of the immunogobulin and integrin supergene families. Cell 52, 925- 33
Streit, W. J., Graeber, M. B. & Kreutzberg, G. W. (1998) Functional plasticity of microglia: a review. Glia 1, 301- 7.
Tran, E. H., Hardin-Pouzet, H., Verge, G. & Owens, T. (1997) Astrocytes and microglia express inducible nitric oxide synthase in mice with experimental allergic encephalomyelitis. Journal of Neuroimmunology 74, 121- 9.
Verbeek, M. M., Otte-Hvller, I., Westphal, J. R., Wesseling, P., Ruiter, D. J., & De Waal, R. M. (1994) Accumulation of intercellular adhesion molecule-1 in senile plaques in brain tissue of patients with Alzheimer's disease. American Journal of Pathology 144, 104- 16.
Wacholtz, M. C., Patel, S. S. & Lipsky, P. E (1989) Leukocyte function-associated antigen 1 is an activation molecule for human T cells. Journal of Experimental Medicine 170, 431- 48.
Watkins, A. D., Hatfield, C. A., Fidler, S. F., Winterrowd, G. E., Brashler, J. R., Sun, F. F., Taylor, B. M., Vonderfecht, S. L., Conder, G. A., Holgate, S. T., Chin, J. E. & Richards, I. M. (1996) Phenotypic analysis of airway eosinophils and lymphocytes in a Th2-driven murine model of pulmonary inflammation. American Journal of Respiratory Cell and Molecular Biology 15, 20- 34.
Watson, C., Whittaker, S., Smith, N., Vora, A. J., Dumonde, D. C. & Brown, K. A. (1996) IL-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes. Clinical and Experimental Immunology 105, 112- 9.
Werner A., Jones L. L., Kloss C. U. A., Neumann H., Wekerle H., Kreutzberg G. W., Raivich G. (1997) Immune Surveillance in the injured CNS: Tlymphocytes invade the axotomized mouse facial motor nucleus and aggregate around sites of neuronal degeneration. Society of Neuroscience Abstracts 23: 283.7.
Yan, Q., Clark, H. B. & Johnson, E. M., Jr. (1990) Nerve growth factor receptor in neural lobe of rat pituitary gland: immunohistochemical localization, biochemical characterization and regulation. Journal of Neurocytology 19, 302- 12.
Zielasek, J., Archelos, J. J., Toyka, K. V & Hartung, H. P. (1993) Expression of intercellular adhesion molecule-1 on rat microglial cells. Neuroscience Letters 153, 136- 9.
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Werner, A., Kloss, C.U.A., Walter, J. et al. Intercellular adhesion molecule-1 (ICAM-1) in the mouse facial motor nucleus after axonal injury and during regeneration. J Neurocytol 27, 219–232 (1998). https://doi.org/10.1023/A:1006928830251
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DOI: https://doi.org/10.1023/A:1006928830251