Migration and Proliferation of Mononuclear Phagocytes in the Central Nervous System

  • Michel Mallat
  • Charles-Félix Calvo
  • Alexandre Dobbertin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 429)


Microglia are resident CNS cells expressing markers of mononuclear phagocytes (Perry, 1994a). Transformation of the microglial phenotype is a hallmark of CNS injuries. This process defined as microglial activation was described in virtually all human neuropathologies, including neurodegenerative diseases, multiple sclerosis and HIV infection (Dickson et al., 1993; McGeer et al., 1993; Kreutzberg 1996).


Human Immunodeficiency Virus Type Experimental Autoimmune Encephalomyelitis Microglial Cell Monocyte Chemoattractant Protein Mononuclear Phagocyte 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Alliot F, Lecain E, Grima B and Pessac B (1991). Microglial progenitors with a high proliferative potential in the embryonic and adult mouse brain. Proc Nail Accra’ Sci USA 88: 1541–1545.CrossRefGoogle Scholar
  2. Aloisi F, Care A, Borsellino G, Gallo P, Rosa S, Bassani A, Cabibbo A, Testa U, Levi G and Peschle C (1992). Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1B and tumor necrosis factor-a. J Immunol 149: 2358–2366.PubMedGoogle Scholar
  3. Appel K, Buttini M, Sauter A and Gebicke-Haerter J (1995). Cloning of rat interleukin-3 receptor ß-subunit from cultured microglia and its mRNA expression in vivo. J Neurosci 15: 5800–5809.PubMedGoogle Scholar
  4. Baggiolini M, Dewalt B and Mosser (1994). Interleukin-8 and related chemotactic cytokines CXC and CC chemokines. Adv Immunol 55: 97–179.PubMedCrossRefGoogle Scholar
  5. Bell MD, Taub DD and Perry VH (1996). Overriding the brain’s intrinsic resistance to leukocyte recruitment with intraparenchymal injections of recombinant chemokines. Neuroscience 74: 283–292.PubMedCrossRefGoogle Scholar
  6. Berezovskaya O., Maysinger D and Fedoroff S (1995). The hematopoietic cytokine colony-stimulating factor in the CNS: Congenital absence of CSF-I in mice results in abnormal microglial response and increased neuron vulnerability to injury. Int JDevl Neurosci 13: 285–299.CrossRefGoogle Scholar
  7. Berman JW, Guida MP, Warren J, Amat J and Brosnan CF (1996). Localization of monocyte chemoattractant peptide-1 expression in the central nervous system in experimental autoimmune encephalomyelitis and trauma in the rat. J Immunol 156: 3017–3023.PubMedGoogle Scholar
  8. Calvo CF, Yoshimura T, Gelman M and Mallat M (1996a). Production of monocyte chemotactic peptide-1 by rat brain macrophages. Eur J Neurosci 8: 1725–1734.PubMedCrossRefGoogle Scholar
  9. Calvo CF and Mallat M (1996b). Expression of macrophage chemotactic protein-I in rat glial cells. In Biology and Physiology of the Blood-Brain Barrier, eds P Couraud and D Sherman, Plenum Press, New York pp 271–277.CrossRefGoogle Scholar
  10. Cecchini MG, Dominguez MG, Mocci S, Wetterwald A, Félix R, Fleisch H, Chilsholm O. Hofstetter W, Pollard JW and Stanley ER (1994). Role of colony stimulating factor-I in the establishment and regulation of tissue macrophages during postnatal development of the mouse. Development 120: 1357–1372.Google Scholar
  11. Chamak B, Dobbertin A and Mallat M (1995). Immunohistochemical detection of thrombospondin in microglia in the developing rat brain. Neuroscience 69: 177–187.PubMedCrossRefGoogle Scholar
  12. Chamak B, Morandi V and Mallat M (1994). Brain macrophages stimulate neurite growth and regeneration by secreting thrombospondin. J Neumsci Res 38: 221–233.CrossRefGoogle Scholar
  13. Chang Y, Albright S and Lee F (1994). Cytokines in the central nervous system: expression of macrophage colony stimulating factor and its receptor during development. J Neuroimmunol 52: 9–17.PubMedCrossRefGoogle Scholar
  14. Coffey PJ, Perry VH and Rawlins JNP (1990). An investigation into the early stages of the inflammatory response folloing ibotenic acid-induced neuronal degeneration. Neuroscience 35: 121–132.PubMedCrossRefGoogle Scholar
  15. Constam DB, Philipp J, Malipiero UV, Ten Dijke P, Schachner M and Fontana A (1992). Differential expression of transforming growth factor-131, -02, and -ß3 by glioblastoma cells, astrocytes, and microglia. J Immunol 148: 1404–1410.PubMedGoogle Scholar
  16. Cuadros MA, Martin C, Coltey MC, Almendros A and Navascuez J (1993) First appearance distribution and origin of macrophages in the early avian development of the avian central nervous system. J. Comp Neural 330: 113–129.CrossRefGoogle Scholar
  17. Dickson DW, Lee SC, Mattiace LA, Yen SC and Brosnan C (1993) Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer’s disease. GLIA 7: 75–83.Google Scholar
  18. Dobbertin A., Schmid P., Gelman M., Glowinski J. and Mallat M. Neurons promote macrophage growth by producing TGF-ß2. Submitted Google Scholar
  19. Elkabes S, DiCicco-Bloom M and Black IB (1996). Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and fuction. J Neurosci 16: 2508–2521.PubMedGoogle Scholar
  20. Epstein LG and Gendelman HE (1993). Human immunodeficiency virus type I infection of the nervous system: pathogenetic mechanisms. Ann Neu-ol 33: 429–436.CrossRefGoogle Scholar
  21. Flaumenhaft R, Kojima S, Abe M and Rifkin DB (1993) Activation of latent transforming growth factor 0. Adv Pharmacol 24: 51–76.PubMedCrossRefGoogle Scholar
  22. Fuentes ME, Durham SK, Swerdel MR, Lewin AC, Barton DS, Megill JR, Bravo R and Lira SA. (1995). Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1.1 Immunol 155: 5769–5776.Google Scholar
  23. Gallo P, De Rossi A. Sivieri s, Chieco-Bianchi L and Tavolato B (1994) M-CSF production by HIV-1-infected monocytes and its intrathecal synthesis. Implications for nerological 11IV-1-related disease. J Neuroimmunol 51: 193–198.PubMedCrossRefGoogle Scholar
  24. Gebicke-Haerter PJ, Appel K, Taylor GD, Schobert A, Rich IN, Northoff H and Berger M (1994). Rat microglial interleukin-3. J Neuroimmunol 50: 203–214.Google Scholar
  25. Gehrmann J. and Kreutzberg G.W. (1995a) Microglia in experimental neuropathology. In °Neuroglia“ eds H. Kettenmann and Ransom B.R. Oxford University Press pp 883–904.Google Scholar
  26. Gehrmann J, Matsumoto Y, Kreutzberg GW (19956) Microglia: intrinsic immuneffector cell of the brain. Brain Res Rev 20: 269–287.Google Scholar
  27. Giulian D., Chen J., Ingeman J.E, George J.K. and Noponen M. (1989) The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain. J Neurosci 9, 4416–4429.PubMedGoogle Scholar
  28. Giulian D, Haverkamp LI, Yu JH, Karshin W, Tom D, Li J, Kirkpatrick J, Kuo YM and Roher AE (1996). SpecificGoogle Scholar
  29. domains of ß-amyloid from Alzheimer plaque elicit neuron killing in human microglia. J Neurosci 16, 6021–6037.Google Scholar
  30. Giulian D and Ingeman J (1988a) Colony-stimulating factors as promoters of ameboid microglia. J Neurosci 8: 4707–4717.PubMedGoogle Scholar
  31. Giulian, D T and Robertson C (1990) Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Ann. Neurol. 27: 33–42.PubMedCrossRefGoogle Scholar
  32. Giulian D, Young DG, Woodward J, Brown DC and Lachman L.B. (1988b) Interleukin-I is an astroglial growth factor in the developing brain. J. Neurosci. 8: 709–714.PubMedGoogle Scholar
  33. Glabinski AR, Balasingam V, Tani M, Kunkel SL, Strieter RM, Yong VW and Ransohoff-RM (1996). Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain. J Immunol 156: 4363–4368.PubMedGoogle Scholar
  34. Godiska R, Chantry D, Dietsch GN and Gray PW (1995) Chemokine expression in murine experimental allergic encephalomyelitis. J Neuroimmunol 58: 167–168.Google Scholar
  35. Hao C, Guilbert LJ and Fedoroff S (1990) Production of colony-stimulating factor-I (CSF-1) by mouse astroglia in vitro. JNeurosci Res 27: 314–323.CrossRefGoogle Scholar
  36. Hayashi M, Luo Y, Laning J, Strieter BM and Dorf ME (1995). Production and function of monocyte chemoattractant protein- I and other b-chemokines in murine glial cells. J Neuroimmunol 60: 143–150.PubMedCrossRefGoogle Scholar
  37. Hickey W, Kimura H (1988) Perivascular microglial cells of the CNS are bone-derived and present antigen in vivo. Science 239: 290–292.PubMedCrossRefGoogle Scholar
  38. Hulkower K, Brosnan CF, Aquino DA, Cammer W, Kulshrestha S, Guida MP, Rapoport DA and Berman JW (1993). Expression of CSF-1, c-fms, and MCP-1 in the central nervous system of rats with experimental allergic encephalomyelitis. J Immunol 6: 2525–2533.Google Scholar
  39. Hurwitz AA, Lyman WD and Berman JW (1995). Tumor necrosis factor-alpha and transforming growth factor-b upregulate astrocyte expression of monocyte chemoattractant protein-1. J Neuroimmunol 57: 193–198.PubMedCrossRefGoogle Scholar
  40. Karpus WJ, Lukacs NW, McRae BL, Strieter RM, Kunkei SL and Miller SD (1995). An important role for the chemokine macrophage inflammatory protein-la in the pathogenesis of T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis. J Immunol 155: 5003–5010.PubMedGoogle Scholar
  41. Kim JS, Gautam SC, Chopp M, Zaloga C, Jones ML, Ward PA and Welch KMA. (1995). Expression of monocyte chemoattractant protein-I and macrophage inflammatory protein-I after focal cerebral ischemia in the rat. J Neuroimmunol 56: 127–134.PubMedCrossRefGoogle Scholar
  42. Kreutzberg GW (1996). Microglia: a sensor for pathological events in the CNS TINS 9: 312–331.Google Scholar
  43. Krieglstein K, Rufer M, Suter-crazzolara C and Unsicker K (1995) Neural functions of the transforming growth factors B. lnt J Devl Neurosci 13: 301–315.CrossRefGoogle Scholar
  44. Kuratsu Jl, Leonard EJ and Yoshimura T (1989). Production and characterization of human gioma-cell derived monocyte chemotactic factor. J Nail Cancer Inst 81: 347–351.CrossRefGoogle Scholar
  45. Lee SC, Liu W, Roth P, Dickson DW, Berman JW, Brosnan CF (1993). Macrophage colony-stimulating factor in fetal astrocytes and microglia: differential regulation by cytokines and lipopolysaccharide and modulation of class ll MHC on microglia J Immunol 150: 594–604.PubMedGoogle Scholar
  46. Ling EA, Wong WC (1993) The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. GLIA 7: 9–18.PubMedCrossRefGoogle Scholar
  47. Logan A, Berry M, Gonzalez AM, Frautschy A, Sporn MB and Baird A (1994) Effects of transforming growth factor ß I on scar production in the injured central nervous system of the rat. Eur J Neurosci 6: 355–363.PubMedCrossRefGoogle Scholar
  48. Malipiero UV, Frei K and Fontana A (1990) Production of hemopoietic colony-stimulating factors by astrocytes. J Immunol 144: 3816–3821.PubMedGoogle Scholar
  49. Mallat M and Chamak B (1994) Brain macrophages: neurotoxic or neurotrophic effector cells ?. J Leukoc Biol 56: 416–422.PubMedGoogle Scholar
  50. Mansfield PJ and Suchard SJ (1994). Thrombospondin promotes chemotaxis and haptotaxis of human peripheral blood monocytes. J Immunol 153: 4219–4229.PubMedGoogle Scholar
  51. Marty S, Dusart 1 and Peschanski M (1991) Glial changes following an excitotoxic lesion in the CNS-I. Microglia/ Macrophages. Neuroscience 45: 529–539.Google Scholar
  52. McGeer PL, Kawamata T, Walker DG, Akiyama H, Tooyama 1, McGeer EG (1993) Microglia in degenerative neurological disease. GLIA 7: 84–92.PubMedCrossRefGoogle Scholar
  53. Meda L, Bernasconi S, Bonaiuto C, Sozzani S, Zhou D, Otvos L, Mantovani A, Rossi F, Cassatella MA. (1996) 1.3amyloid (25–35) peptide and IFN-g synergistically induce the production of chemeotactic cytokine MCP1/JE in monocytes and microglial cells. J Immunol 157: 1213–1218.Google Scholar
  54. Merrill J.E. (1992). Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain development: normal and pathological. Devl Neurosci 14: 1–10.CrossRefGoogle Scholar
  55. Metcalf D (1989) The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature 339: 27–30.PubMedCrossRefGoogle Scholar
  56. Michaelson M.D., Bieri P.L., Mehler M.F., Xu H., Arezzo J.C., Pollard J.W and Kessler J.A. (1996) CSF-1 deficiency in mice results in abnormal brain development. Development 122, 2661–2672.PubMedGoogle Scholar
  57. Morgan TE, Nichols NR, Pasinetti GM and Finch CE (1993) TGF-ßl mRNA increases in macrophages/ microglial cells of the hippocampus in response to deafferentation and kainic acid-induced neurodegeneration. Exp Neurol 120: 291–301.PubMedCrossRefGoogle Scholar
  58. Murphy GM, Jia JX, Song Y, Ong E, Shrivastava R, Bocchini V, Lee YL and Eng LF (1995). Macrophage inflammatory protein 1-a mRNA expression in a immortalized microglial cell line and cortical astrocyte cultures. J Neurosci res 40: 755–763.PubMedCrossRefGoogle Scholar
  59. Nohava K, Malipiero U, Frei K and Fontana A (1992) Neurons and neuroblastoma as a source of macrophage colony-stimulating factor. EurJlmmunol22: 2539–2545.Google Scholar
  60. Perry V.H. (1994a). Microglia, resident macrophages of the CNS. In “Macrophages and the nervous system” ed MBIT, RG Landes Company, CRC Press. pp 6–27.Google Scholar
  61. Perry VH, Lawson LJ, Reid DM (1994b). Biology of the mononuclear phagocyte system of the central nervous system and HIV infection. J Leukoc Biol 56: 399–406.PubMedGoogle Scholar
  62. Raivich G, Moreno-Flores MT, Möller JC and Kreutzberg GW (1994). Inhibition ofposttraumatic microglial proliferation in a genetic model of macrophage colony-stimulating factor defiency in the mouse. Eon J Neurosci 6: 1615–1618.CrossRefGoogle Scholar
  63. Ransohoff RM, Hamilton TA, Tanie M, Stoler MH, Schick HE, Major JA, Estes ML, Thomas DM and Tuohy VK (1993). Astrocyte expression of mRNA encoding IP-10 and JE/MCP-I in experimental autoimmune encephalomyelitis. FASEBJ7: 592–600.Google Scholar
  64. Rinner WA, Bauer J, Schmidts M, Lassmann H and Hickey WF (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
  65. Roth P and Stanley ER (1992). The biology of CSF-1 and its receptor. Curr Top Microbiol Immunol 181: 141–167.PubMedCrossRefGoogle Scholar
  66. Roth P and Stanley ER (1996). Colony stimulating factor-1 expression is developmentally regulated in the mouse. J Leukoc Biol 59: 817–823.PubMedGoogle Scholar
  67. Sakanashi Y, Takeya M, Yoshimura T, Feng L, Morioka T and Takahashi K (1994). Kinetics of macrophage sub-populations and expression of monocyte chemoattractant protein-I (MCP-1) in bleomycin-induced lung injury of rats studied by a novel monoclonal antibody against rat MCP-1. J Leukoc Biol 56: 741–750.PubMedGoogle Scholar
  68. Schmidtmayerova H, Nottet HS, Nuovo G, Raabe T, Flanagan CR, Dubrovsky L, Gendelman HE, Cerami A, Bukrinsky M and Sherry B (1996). Human immunodeficiency virus type 1 infections alters chemokine beta peptide expression in human monocyte: implications for recruitment of leukocytes into brain and lymph nodes. Proc Natl Acad Sci USA 93: 700–704.Google Scholar
  69. Schultz-Cherry S and Murphy-Ullrich JE (1993). Thrombospondin causes activation of latent transforming growth factor-ß secreted by endothelial cells by a novel mechanism. J Cell Biol 122, 923–932.PubMedCrossRefGoogle Scholar
  70. Streit WJ and Kreutzberg GW (1987). Lectin binding by resting and reactive microglia. J Neurocytol 16: 249–260.PubMedCrossRefGoogle Scholar
  71. Streit WJ and Kreutzberg GW (1988). Response of endogenous glial cells to motor neuron degeneration induced by toxin ricin. J Comp Neurol 268: 248–263.PubMedCrossRefGoogle Scholar
  72. Thanos, S., Mey, J. and Wild, M. (1993) Treatment of the adult retina with microglia-suppressing factors retards axotomy-induces neuronal degradation and enhances axonal regeneration in vivo and in vitro. J Neurosci 13, 455–466.Google Scholar
  73. Théry C, Flétier E, Evrard C and Mallat M (1990) Expression of macrophage colony-stimulating factor gene in the mouse brain during development. J Neurosci Res 26: 129–133.Google Scholar
  74. Théry C, Stanley ER, Mallat M (1992) Interleukin 1 and tumor necrosis factor-a stimulate the production of colony-stimulating factor 1 by murine astrocytes. J Neurochem 59: 1183–1186.PubMedCrossRefGoogle Scholar
  75. Wahl SM, Allen JB, McCartney-Francis N, Morganati-Kossmann MC, Kossmann T, Ellingsworth L, Ma UEH, Mergenhagen SE and Orenstein JM (1991). Macrophage-and astrocyte-derived transforming growth factor-ß as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome J Exp Med 173: 981–991.PubMedCrossRefGoogle Scholar
  76. Wahl SM, Hunt DA, Wakefield L, Mc Cartney -Francis N, Wahl LM, Roberts AB, Sporn MB (1987) Transforming growth factor beta (TGF-ß) induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 84: 5788–5792.PubMedCrossRefGoogle Scholar
  77. Wiktor-Jedrzejczak, W, Bartocci A, Ferrante AW, Ahmed-Ansarì A, Sell KW, Pollard JW and Stanley ER (1990) Total absence of colony-stimulating factor 1 in the macrophage deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci USA 87: 4828–4832.PubMedCrossRefGoogle Scholar
  78. Witmer-Pack MD, Hughes DA, Schuler G, Lawson L, McWilliam A, Inaba K, Steinman RM and Gordon S (1993). Identification of macrophages and dendritic cells in the osteopetrotic (op/op) mouse. J Cell Sci 104: 1021–1029.PubMedGoogle Scholar
  79. Yao J, Harvath L, Guilbert DL, Colton CA (1990) Chemotaxis by a CNS macrophage, the microglia. J. Neurosci Res 27: 36–42.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Michel Mallat
    • 1
  • Charles-Félix Calvo
    • 1
  • Alexandre Dobbertin
    • 1
  1. 1.INSERM U.114, Chaire de NeuropharmacologieCollège de FranceParis Cedex 05France

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