Abstract
The morphology, distribution and immunophenotype of microglia throughout the adult rat hypothalamo-neurohypophysial system was examined. Four macrophage-associated antibodies (OX-42, F4/80, ED1 and ED2) were used; the expression of major histocompatibility complex antigens was investigated by use of antibodies against OX-6, OX-17 (MHC class II) and OX-18 (MHC class I). Three distinct types of microglia were identified. The first was located in the magnocellular nuclei; these ‘radially branched’ (‘ramified’) microglia had round cell bodies and long branched processes, and were strongly immunoreactive only for OX-42. The second was located outside the blood-brain barrier in the median eminence, pituitary stalk and neurohypophysis often close to blood vessels; these ‘compact’ microglia had irregular cell bodies and shorter processes, and were strongly labelled by OX-42 and F4/80, weakly labelled by OX-18, and generally unlabelled by ED1, ED2, OX-6 and OX-17. The third type was found in small numbers throughout the system at the surface of the neurvous tissue or around blood vessels; these ‘perivascular’ microglia were elongated cells with no branching processes, and were strongly labelled by ED1, ED2, OX-18, OX-6, OX-17 and F4/80 antibodies but showed variable OX-42 immunoreactivity. Cells in a perivascular location were heterogeneous with respect to their immunophenotype. The presence in the normal adult rat hypothalamo-neurohypophysial system of MHC class-II molecules (OX-6 and OX-17) on a sub-set of perivascular microglia suggests that these cells are capable of presenting antigen to T lymphocytes. The microglia, which lie on either side of the blood-brain barrier, are well placed to facilitate interaction between the immune and neuroendocrine systems.
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References
Barbé E, Damoiseaux JGMC, Döpp EA, Dijkstra CD (1990) Characterisation and expression of the antigen present on resident rat macrophages recognised by monoclonal antibody ED2. Immunobiology 182:88–99
Bignami A, Eng LF, Dahl D, Uyeda CT (1972) Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res 43:429–435
Bo L, Mork S, Kong PA, Nyland H, Pardo CA, Trapp BD (1994) Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions. J Neuroimmunol 51:135–146
Dijkstra CD, Damoiseaux JGMC (1993) Macrophage heterogeneity established by immunocytochemistry. Prog Histochem Cytochem 27:1–65
Dijkstra CD, Döpp EA, Joling P, Kraal G (1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognised by monoclonal antibodies ED1, ED2 and ED3. Immunology 54:589–599
Fukomoto T, McMaster WR, Williams AF (1982) Mouse monoclonal antibodies against rat major histocompatibility antigens. Two Ia antigens and expression of Ia and class I antigens in rat thymus. Eur J Immunol 12:237–243
Gehrmann J, Banati RB, Kreutzberg GW (1993a) Microglia in the immune surveillance of the brain: human microglia constitutively express HLA-DR molecules. J Neuroimmunol 48:189–198
Gehrmann J, Mies G, Bonnekoh P, Banati R, Iijima T, Kreutzberg GW, Hossmann KA (1993b) Microglial reaction in the rat cerebral cortex induced by cortical spreading depression. Brain Pathol 3:11–17
Graeber MB, Streit WJ, Kreutzberg GW (1989) Identity of ED2-positive perivascular cells in rat brain. J Neurosci Res 22:103–106
Graeber MB, Streit WJ, Büringer D, Sparks DL, Kreutzberg GW (1992) Ultrastructural location of major histocompatibility complex (MHC) class II positive perivascular cells in histologically normal human brain. J Neuropathol Exp Neurol 51:303–311
Hickey WF, Kimura H (1988) Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239:290–292
Konno H, Yamamoto T, Iwasaki Y, Saitoh T, Suzuki H, Terunuma H (1989) Ia-expressing microglial cells in experimental allergic encephalomyelitis in rats. Acta Neuropathol 77:472–479
Lawson LJ, Perry VH, Dri P, Gordon S (1990) Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39:151–170
Mander TH, Morris JF (1993) Activity of perivascular microglia in the rat neural lobe. Ann NY Acad Sci 689:554–558
Mander TH, Morris JF (1994) Perivascular microglia in the rat neural lobe engulf magnocellular secretory terminals during osmotic stimulation. Neurosci Lett 180:235–238
McCombe PA, Jersey J de, Pender MP (1994) Inflammatory cells, microglia and MHC class II antigen-positive cells in the spinal cord of Lewis rats with acute and chronic relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol 51:153–167
McLean IW, Nakane PK (1974) Periodate-lysine-paraformaldehyde fixative a new fixative for immunoelectron microscopy. J Histochem Cytochem 22:1077–1083
McMaster WR, Williams AF (1979) Identification of Ia glycoproteins in rat thymus and purification from rat spleen. Eur J Immunol 9:426–433
Milligan CE, Cunningham TJ, Levitt P (1991) Differential immunochemical markers reveal the normal distribution of brain macrophages and microglia in the developing rat brain. J Comp Neurol 314:124–135
Moffett CW, Paden CM (1994) Microglia in the rat neurohypophysis increase expression of class I major histocompatibility antigens following central nervous system injury J Neuroimmunol 50:139–151
Morioka T, Kalehua AN, Streit WJ (1992) Progressive expression of immunomolecules on microglial cells in rat dorsal hippocampus following transient forebrain ischaemia. Acta Neuropathol 83:590–597
Olivieri-Sangiacomo C (1972) On the fine structure of the perivascular cells in the neural lobe of rats. Z Zellforsch 132:25–34
Perry VH, Gordon S (1987) Modulation of CD4 antigen on macrophages and microglia in rat brain. J Exp Med 166:1138–1143
Perry VH, Lawson LJ (1992) Macrophages in the central nervous system. In: Lewis CE, McGee JO'D (eds) The macrophage. Oxford University Press, Oxford New York Tokyo, pp 391–413
Perry VH, Hume DA, Gordon S (1985) Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15:313–326
Perry VH, Crocker PR, Gordon S (1992) The blood-brain barrier regulates the expression of a macrophage sialic acid-binding receptor on microglia. J Cell Sci 101:201–207
Pow DV, Perry VH, Morris JF, Gordon S (1989) Microglia in the neurohypophysis associate with and endocytose terminal portions of neurosecretory neurons. Neuroscience 33:567–578
Robinson AP, White TM, Mason DW (1986) Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunology 57:239–247
Salm AK, Hatton GI, Nilaver G (1982) Immunoreactive glial fibrillary acidic protein in pituicytes of the rat neurohypophysis. Brain Res 236:471–476
Sasaki A, Hirato J, Nakazato Y (1993) Immunohistochemical study of microglia in the Creutzfeldt-Jakob diseased brain. Acta Neuropathol (Berl) 86:337–344
Starkey PM, Turley L, Gordon S (1987) the mouse macrophagespecific glycoprotein defined by monoclonal antibody F4/80: characterisation, biosynthesis and demonstration of a rat analogue. Immunology 60:117–122
Streit WJ, Graeber MB, Kreutzberg GW (1989) Expression of Ia antigen on perivascular and microglial cells after sublethal and lethal motor neuron injury. Exp Neurol 105:115–126
Thomas WE (1992) Brain macrophages: evaluation of microglia and their functions. Brain Res Rev 17:61–74
Troost D, Claessen N, Oord JJ van den, Swaab DF, Jong JM de (1993) Neuronophagia in the motor cortex in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 9:390–397
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Mander, T.H., Morris, J.F. Immunophenotypic evidence for distinct populations of microglia in the rat hypothalamo-neurohypophysial system. Cell Tissue Res 280, 665–673 (1995). https://doi.org/10.1007/BF00318369
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DOI: https://doi.org/10.1007/BF00318369