Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-27T20:05:15.613Z Has data issue: false hasContentIssue false
  • English
  • Français

MHC class II expression by β2 integrin (CD18)-positive microglia, macrophages and macrophage-like cells in rabbit retina

Published online by Cambridge University Press:  06 July 2009

Wenbing Huang ,
Coral G. Chamberlain ,
Richard Y. Sarafian  and
Tailoi Chan-Ling
Wenbing Huang
Affiliation:
School of Medical Sciences (Anatomy and Histology) and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia
Coral G. Chamberlain
Affiliation:
School of Medical Sciences (Anatomy and Histology) and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia
Richard Y. Sarafian
Affiliation:
School of Medical Sciences (Anatomy and Histology) and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia
Tailoi Chan-Ling*
Affiliation:
School of Medical Sciences (Anatomy and Histology) and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia
*
Correspondence should be addressed to: Tailoi Chan-Ling, Anatomy and Histology (F13), School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia phone: +61 2 9351 2596 fax: +61 2 9351 6556 email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

The aim of this study was to investigate the developmental expression of major histocompatibility complex class II (MHCII) by microglia and macrophages and their relationship to blood vessels in the retina, a representative tissue of the central nervous system. Such information is crucial to understanding the role of these cells in immune surveillance. Wholemount preparations of retinas from late embryonic, postnatal and adult rabbits were subjected to three-colour fluorescence microscopy using β2 integrin (CD18) and MHCII antibodies and biotinylated Griffonia simplicifolia B4 isolectin labelling of blood vessels. CD18+ cells consistently exhibited characteristics of macrophages or microglia in the vascularized and non-vascularized regions of the retina, respectively. At all ages, MHCII was expressed by a high proportion of cells in the vascularized region, which contained macrophage-like ‘parenchymal cells’ as well as typical perivascular macrophages. MHCII expression by ramified microglia, first detected on postnatal day 30, was lower in the peripheral retina and intermediate in the avascular region of the myelinated streak. The observed localization of MHCII+ cells in relation to blood vessels and location-dependent differences in MHCII expression point to the possibility that these cells may be distributed strategically within the retina to provide multiple lines of defence against immune challenge arriving via the retinal vasculature.

Keywords

Central nervous systemimmune systemglial cellsretinal macrophagesimmunohistochemistry
Type
Research Article
Information
Neuron Glia Biology , Volume 4 , Issue 4 , November 2008 , pp. 285 - 294
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Ambati, J., Ambati, B.K., Yoo, S.H., Ianchulev, S. and Adamis, A.P. (2003) Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Survey of Ophthalmology 48, 257–293.CrossRefGoogle ScholarPubMed
Ashwell, K. (1989) Development of microglia in the albino rabbit retina. Journal of Comparative Neurology 287, 286–301.CrossRefGoogle ScholarPubMed
Becher, B., Prat, A. and Antel, J.P. (2000) Brain-immune connection: immuno-regulatory properties of CNS-resident cells. Glia 29, 293–304.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Bosco, A., Inman, D.M., Steele, M.R., Wu, G., Soto, I., Marsh-Armstrong, N. et al. (2008) Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma. Investigative Ophthalmology and Visual Science 49, 1437–1446.CrossRefGoogle ScholarPubMed
Chan-Ling, T. (1994) Glial, neuronal and vascular interactions in the mammalian retina. Progress in Retinal and Eye Research 13, 357–389.CrossRefGoogle Scholar
Chan-Ling, T. (1997) Glial, vascular, and neuronal cytogenesis in whole-mounted cat retina. Microscopy Research and Technique 36, 1–16.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Chan-Ling, T. (2006) The blood retinal interface: similarities and contrasts with the blood-brain barrier. In Dermietzel, R., Spray, D.C. & Needergard, M. (eds) Blood-Brain Interfaces: From Ontogeny to Artificial Barriers. Weinheim: Wiley-VCH, pp. 701–724.CrossRefGoogle Scholar
Chan-Ling, T., Halasz, P. and Stone, J. (1990) Development of retinal vasculature in the cat: stages, topography and mechanisms. Current Eye Research 9, 459–478.CrossRefGoogle ScholarPubMed
Chan-Ling, T. and Stone, J. (1991) Factors determining the shape, spacing and distribution of astrocytes in the cat retina: the contact-spacing model of astrocyte interaction. Journal of Comparative Neurology 303, 387–399.CrossRefGoogle Scholar
Checchin, D., Sennlaub, F., Levavasseur, E., Leduc, M. and Chemtob, S. (2006) Potential role of microglia in retinal blood vessel formation. Investigative Ophthalmology and Visual Science 47, 3595–3602.CrossRefGoogle ScholarPubMed
Chen, L., Yang, P. and Kijlstra, A. (2002) Distribution, markers, and functions of retinal microglia. Ocular Immunology and Inflammation 10, 27–39.CrossRefGoogle ScholarPubMed
Chu, Y., Hughes, S. and Chan-Ling, T. (2001) Differentiation and migration of astrocyte precursor cells and astrocytes in human fetal retina: relevance to optic nerve coloboma. FASEB Journal 15, 2013–2015.CrossRefGoogle ScholarPubMed
Cuff, C.A., Berman, J.W. and Brosnan, C.F. (1996) The ordered array of perivascular macrophages is disrupted by IL-1-induced inflammation in the rabbit retina. Glia 17, 307–316.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
Dick, A.D., Ford, A.L., Forrester, J.V. and Sedgwick, J.D. (1995) Flow cytometric identification of a minority population of MHC class II positive cells in the normal rat retina distinct from CD45lowCD11b/c+CD4low parenchymal microglia. British Journal of Ophthalmology 79, 834–840.CrossRefGoogle ScholarPubMed
Fabriek, B.O., Van Haastert, E.S., Galea, I., Polfliet, M.M.J., Döpp, E.D., Van Den Heuvel, M.M. et al. (2005) CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation. Glia 51, 297–305.CrossRefGoogle ScholarPubMed
Galea-Lauri, J., Blackford, J. and Wilkinson, J.M. (1993) The expression of CD11/CD18 molecules on rabbit leucocytes: identification of monoclonal antibodies to CD18 and their effect on cellular adhesion processes. Molecular Immunology 30, 529–537.CrossRefGoogle ScholarPubMed
Gaucher, D., Chiappore, J.A., Paques, M., Simonutti, M., Boitard, C., Sahel, J.A. et al. (2007) Microglial changes occur without neural cell death in diabetic retinopathy. Vision Research 47, 612–623.CrossRefGoogle ScholarPubMed
Gehrmann, J., Matsumoto, Y. and Kreutzberg, G.W. (1995) Microglia: intrinsic immunoeffector cell of the brain. Brain Research Reviews 20, 269–287.CrossRefGoogle Scholar
Graeber, M.B. (1993) Microglia, macrophages and the blood-brain barrier. Clinical Neuropathology 12, 296–297.Google ScholarPubMed
Graeber, M.B., Bise, K. and Mehraein, P. (1994) CR3/43, a marker for activated human microglia: application to diagnostic neuropathology. Neuropathology and Applied Neurobiology 20, 406–408.CrossRefGoogle ScholarPubMed
Graeber, M.B. and Streit, W.J. (1990) Microglia: immune network in the CNS. Brain Pathology 1, 2–5.CrossRefGoogle ScholarPubMed
Hanisch, U.K. and Kettenmann, H. (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nature Neuroscience 10, 1387–1394.CrossRefGoogle ScholarPubMed
Hayes, G.M., Woodroofe, M.N. and Cuzner, M.L. (1988) Microglia express MHC class II in normal and demyelinating human white matter. Annals of the New York Academy of Sciences 540, 501–503.CrossRefGoogle ScholarPubMed
Hickey, W.F. and Kimura, H. (1988) Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239, 290–292.CrossRefGoogle ScholarPubMed
Hollyfield, J.G., Bonilha, V.L., Rayborn, M.E., Yang, X., Shadrach, K.G., Lu, L. et al. (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nature Medicine 14, 194–198.CrossRefGoogle ScholarPubMed
Hu, P., Pollard, J., Hunt, N. and Chan-Ling, T. (1998a) Microvascular and cellular responses in the retina of rats with acute experimental allergic encephalomyelitis (EAE). Brain Pathology 8, 487–498.CrossRefGoogle ScholarPubMed
Hu, P., Pollard, J., Hunt, N., Taylor, J. and Chan-Ling, T. (1998b) Microvascular and cellular responses in the optic nerve of rats with acute experimental allergic encephalomyelitis (EAE). Brain Pathology 8, 475–486.CrossRefGoogle ScholarPubMed
Hu, P., Pollard, J.D. and Chan-Ling, T. (2000) Breakdown of the blood-retinal barrier induced by activated T cells of nonneural specificity. American Journal of Pathology 156, 1139–1149.CrossRefGoogle ScholarPubMed
Humphrey, M.F. and Moore, S.R. (1995) Strain differences in the distribution of NDP-ase labelled microglia in the normal rabbit retina. Glia 15, 367–376.CrossRefGoogle ScholarPubMed
Kalsow, C.M. and Dwyer, A.E. (1998) Retinal immunopathology in horses with uveitis. Ocular Immunology and Inflammation 6, 239–251.CrossRefGoogle ScholarPubMed
Kloss, C.U., Bohatschek, M., Kreutzberg, G.W. and Raivich, G. (2001) Effect of lipopolysaccharide on the morphology and integrin immunoreactivity of ramified microglia in the mouse brain and in cell culture. Experimental Neurology 168, 32–46.CrossRefGoogle ScholarPubMed
Kulaga, H., Sogn, J.A., Weissman, J.D., Marche, P.N., LeGuern, C., Long, E.O. et al. (1987) Expression patterns of MHC class II genes in rabbit tissues indicate close homology to human counterparts. Journal of Immunology 139, 587–592.CrossRefGoogle ScholarPubMed
Lee, J.E., Liang, K.J., Fariss, R. and Wong, W.T. (2008) Ex vivo dynamic imaging of retinal microglia using time-lapse confocal microscopy. Investigative Ophthalmology and Visual Science 49, 4169–4176.CrossRefGoogle ScholarPubMed
Martin, R. and McFarland, H.F. (1995) Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis. Critical Reviews in Clinical Laboratory Sciences 32, 121–182.CrossRefGoogle ScholarPubMed
Matsubara, T., Pararajasegaram, G., Wu, G.S. and Rao, N.A. (1999) Retinal microglia differentially express phenotypic markers of antigen-presenting cells in vitro. Investigative Ophthalmology and Visual Science 40, 3186–3193.Google ScholarPubMed
McMenamin, P.G. and Forrester, J.V. (2001) Dendritic cells in the eye. In Lotze, M.T. & Thomson, A.W. (eds) Dendritic Cells, 2nd ed. San Diego: Academic Press, pp. 398–409.Google Scholar
Medana, I.M., Chan-Ling, T. and Hunt, N.H. (2000) Reactive changes of retinal microglia during fatal murine cerebral malaria: effects of dexamethasone and experimental permeabilization of the blood-brain barrier. American Journal of Pathology 156, 1055–1065.CrossRefGoogle ScholarPubMed
Medana, I.M., Hunt, N.H. and Chan-Ling, T. (1997) Early activation of microglia in the pathogenesis of fatal murine cerebral malaria. Glia 19, 91–103.3.0.CO;2-C>CrossRefGoogle ScholarPubMed
Milner, R. and Campbell, I.L. (2002) The integrin family of cell adhesion molecules has multiple functions within the CNS. Journal of Neuroscience Research 69, 286–291.CrossRefGoogle ScholarPubMed
Morcos, Y. and Chan-Ling, T. (1997) Identification of oligodendrocyte precursors in the myelinated streak of the adult rabbit retina in vivo. Glia 21, 163–182.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
Morcos, Y., Shorey, C.D. and Chan-Ling, L. (1999) Contribution of O4+ oligodendrocyte precursors and astrocytes to the glial ensheathment of vessels in the rabbit myelinated streak. Glia 27, 1–14.3.0.CO;2-M>CrossRefGoogle Scholar
Naskar, R., Wissing, M. and Thanos, S. (2002) Detection of early neuron degeneration and accompanying microglial responses in the retina of a rat model of glaucoma. Investigative Ophthalmology and Visual Science 43, 2962–2968.Google ScholarPubMed
O'Keefe, G.M., Nguyen, V.T. and Benveniste, E.N. (2002) Regulation and function of class II major histocompatibility complex, CD40, and B7 expression in macrophages and microglia: implications in neurological diseases. Journal of Neurovirology 8, 496–512.CrossRefGoogle ScholarPubMed
Penfold, P.L., Liew, S.C., Madigan, M.C. and Provis, J.M. (1997) Modulation of major histocompatibility complex class II expression in retinas with age-related macular degeneration. Investigative Ophthalmology and Visual Science 38, 2125–2133.Google ScholarPubMed
Penfold, P.L., Provis, J.M. and Liew, S.C. (1993) Human retinal microglia express phenotypic characteristics in common with dendritic antigen-presenting cells. Journal of Neuroimmunology 45, 183–191.CrossRefGoogle ScholarPubMed
Provis, J.M., Diaz, C.M. and Penfold, P.L. (1996) Microglia in human retina: a heterogeneous population with distinct ontogenies. Perspectives on Developmental Neurobiology 3, 213–222.Google ScholarPubMed
Provis, J.M., Penfold, P.L., Edwards, A.J. and van Driel, D. (1995) Human retinal microglia: expression of immune markers and relationship to the glia limitans. Glia 14, 243–256.CrossRefGoogle Scholar
Reid, D.M., Perry, V.H., Andersson, P.B. and Gordon, S. (1993) Mitosis and apoptosis of microglia in vivo induced by an anti-CR3 antibody which crosses the blood-brain barrier. Neuroscience 56, 529–533.CrossRefGoogle ScholarPubMed
Schnitzer, J. (1989) Enzyme-histochemical demonstration of microglial cells in the adult and postnatal rabbit retina. Journal of Comparative Neurology 282, 249–263.CrossRefGoogle ScholarPubMed
Schwartz, M. (2007) Modulating the immune system: a vaccine for glaucoma? Canadian Journal of Ophthalmology 42, 439–441.CrossRefGoogle ScholarPubMed
Schwartz, M., Butovsky, O., Bruck, W. and Hanisch, U.-K. (2006) Microglial phenotype: is the commitment reversible? Trends in Neurosciences 29, 68–74.CrossRefGoogle ScholarPubMed
Sedgwick, J.D., Schwender, S., Gregersen, R., Dorries, R. and ter Meulen, V. (1993) Resident macrophages (ramified microglia) of the adult brown Norway rat central nervous system are constitutively major histocompatibility complex class II positive. Journal of Experimental Medicine 177, 1145–1152.CrossRefGoogle ScholarPubMed
Spieker-Polet, H., Sittisombut, N., Yam, P.C. and Knight, K.L. (1990) Rabbit major histocompatibility complex. IV. Expression of major histocompatibility complex class II genes. Journal of Immunogenetics 17, 123–132.CrossRefGoogle ScholarPubMed
Stein, V.M., Czub, M., Hansen, R., Leibold, W., Moore, P.F., Zurbriggen, A. et al. (2004) Characterization of canine microglial cells isolated ex vivo. Veterinary Immunology and Immunopathology 99, 73–85.CrossRefGoogle ScholarPubMed
Stoll, G. and Jander, S. (1999) The role of microglia and macrophages in the pathophysiology of the CNS. Progress in Neurobiology 58, 233–247.CrossRefGoogle ScholarPubMed
Thanos, S., Moore, S. and Hong, Y.-M. (1996) Retinal microglia. Progress in Retinal and Eye Research 15, 331–361.CrossRefGoogle Scholar
Vass, K. and Lassmann, H. (1990) Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system. American Journal of Pathology 137, 789–800.Google ScholarPubMed
Wekerle, H. and Lassmann, H. (1994) Contra: evidence against a primary lesion in the target organ in autoimmune disease. International Archives of Allergy and Immunology 103, 328–331.CrossRefGoogle ScholarPubMed
Wilkinson, J.M., McDonald, G., Smith, S., Galea-Lauri, J., Lewthwaite, J., Henderson, B. et al. (1993) Immunohistochemical identification of leucocyte populations in normal tissue and inflamed synovium of the rabbit. Journal of Pathology 170, 315–320.CrossRefGoogle ScholarPubMed
Williams, K., Alvarez, X. and Lackner, A.A. (2001) Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system. Glia 36, 156–164.CrossRefGoogle ScholarPubMed
Zhang, J., Wu, G.S., Ishimoto, S., Pararajasegaram, G. and Rao, N.A. (1997) Expression of major histocompatibility complex molecules in rodent retina. Immunohistochemical study. Investigative Ophthalmology and Visual Science 38, 1848–1857.Google ScholarPubMed