Summary
To evaluate the usefulness of microglial markers for routine neuropathological material, we studied formalin-fixed, paraffin-embedded human brain tissue with the immunoperoxidase method using the lectinRicinus communis agglutinin (RCA-1) and four monoclonal antibodies (LN-1, LN-2, LN-3, anti-HLA-DR/ alpha). RCA-1 stained resting microglia, but the staining intensity was mostly weak. LN-1 also stained resting microglia in paraffin sections first treated with protease. In contrast to LN-1, RCA-1 stained blood vessels heavily. LN-1 stained resting microglia more markedly than RCA-1 in brains fixed for a prolonged period of time. However, LN-1 recognized a small number of astrocytes in routine paraffin sections. LN-3 reactivity was detected on a few resting microglia, but was intensely expressed on large numbers of reactive microglia in many neurological diseases. Both LN-2 and anti-HLA-DR/alpha labelled microglia, but the reactions were inconsistent. This study suggests that the monoclonal antibodies LN-1 and LN-3 are useful for the demonstration of microglia in paraffin sections, and a combination of these antibodies and the antibody to glial fibrillary acidic protein is recommended in attempting to identify microglia.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chou SM, Miles JM (1989) B-cell immunomarkers recognize rod cells in paraffin sections (abstract) J Neuropathol Exp Neurol 48:344
Dickson DW, Mattiace LA (1989) Astrocytes and microglia in human brain share an epitope recognized by a B-lymphocytespecific monoclonal antibody (LN-1). Am J Pathol 135:135–147
Epstein A, Marder RJ, Winter JN, Fox RI (1984) Two new monoclonal antibodies (LN-1, LN-2) reactive in B5 formalin-fixed, paraffin-embedded tissues with follicular center and mantle zone human B lymphocytes and derived tumors. J Immunol 133:1028–1036
Frank E, Pulver M, Tribolet N de (1986) Expression of class II major histocompatibility antigens on reactive astrocytes and endothelial cells within the gliosis surrounding metastases and abscesses. J Neuroimmunol 12:29–36
Fujita S, Kitamura T (1975) Origin of brain macrophages and the nature of the so-called microglia. Acta Neuropathol (Berl) [Suppl] 6:291–296
Giulian D, Baker TJ, Shih LC, Lachman LB (1986) Interleukin 1 of the central nervous system is produced by ameboid microglia. J Exp Med 164:594–604
Giulian D, Young DG, Woodward J, Brown DC, Lachman B (1988) Interleukin-1 is an astroglial growth factor in the developing brain. J Neurosci 8:709–714
Haga S, Akai K, Ishii T (1989) Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain: an immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol (Berl) 77:569–575
Hayes GW, Woodroofe MN, Cuzner ML (1987) Microglia are the major cell type expressing MHC class II in human white matter. J Neurol Sci 80:25–37
Hickey WF, Kimura H (1988) Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239:290–292
Kaneko Y, Kitamoto T, Tateishi J, Yamaguchi K (1989) Ferritin immunohistochemistry as a marker for microglia. Acta Neuropathol (Berl) 79:129–136
Koch N, Wong GHW, Schrader JW (1984) Ia antigens and associated invariant chain are induced simultaneously in lines of T dependent mast cells by recombinant interferon-γ. J Immunol 132:1361–1369
Ling EA (1981) The origin and nature of microglia. In: Federoff S, Hertz L (eds), Advance in cellular neurobiology, vol 2. Academic Press, New York, pp 33–82
Mannoji H, Yeger H, Becker LE (1986) A specific histochemical marker (lectinRicinus communis agglutinin-1) for normal human microglia, and application to routine histopathology. Acta Neuropathol (Berl) 71:341–343
Marder RJ, Variakojis D, Silver J, Epstein AL (1985) Immunohistochemical analysis of human lymphomas with monoclonal antibodies to B cell and Ia antigens reactive in paraffin sections. Lab Invest 52:497–504
McGeer PL, Itagaki S, McGeer EG (1988) Expression of the histocompatibility glycoprotein HLA-DR in neurological disease. Acta Neuropathol (Berl) 76:550–557
Michaels J, Price RW, Rosenblum MK (1988) Microglia in the giant cell encephalitis of acquired immune deficiency syndrome: proliferation, infection and fusion. Acta Neuropathol (Berl) 76:373–379
Miles JM, Chou SM (1988) A new immunoperoxidase marker for microglia in paraffin section. J Neuropathol Exp Neurol 47:579–587
Miyake T, Tsuchihashi Y, Kitamura T, Fujita S (1984) Immunohistochemical studies of blood monocytes infiltrating into the neonatal rat brain. Acta Neuropathol (Berl) 62:291–297
Nakazato Y, Ishizeki J, Takahashi K, Yamaguchi H, Kamei T, Mori T (1982a) Localization of S-100 protein and glial fibrillary acidic protein-related antigen in pleomorphic adenoma of the salivary glands. Lab Invest 46:621–626
Nakazato Y, Ishizeki J, Takahashi K, Yamaguchi H (1982b) Immunohistochemical localization of S-100 protein in granular cell myoblastoma. Cancer 49:1624–1628
Noelle RJ, Kuziel WA, Maliszewski CR, McAdams E, Vitetta ES, Tucker PW (1986) Regulation of the expression of multiple class II genes in murine B cells by B cell stimulatory factor-1 (BSF-1). J Immunol 137:1718–1723
Oehmichen M, Wietholter H, Greaves MF (1979) Immunological analysis of human microglia: lack of monocytic and lymphoid differentiation antigens. J Neuropathol Exp Neurol 38:99–103
Okon E, Felder B, Epstein A, Lukes RJ, Taylor CR (1985) Monoclonal antibodies reactive with B-lymphocytes and histiocytes in paraffin sections. Cancer 56:95–104
Perry VH, Hume DA, Gordon S (1985) Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15:313–326
Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, Cleary P (1988) The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586–592
Rio-Hortega P del (1920) La microglia y su transformacion en celulas en basoncito y cuerpos granulo-adiposos. Trab Lab Invest Biol Madrid 18:37–82
Rio-Hortega P del (1932) Microglia. In: Penfield W (ed), Cytology and cellular pathology of the nervous system, vol 2. P. Hoeber, New York, pp 481–534
Sasaki A, Levison SW, Ting JP-Y (1989) Comparison and quantitation of Ia antigen expression on cultured macroglia and ameboid microglia from Lewis rat cerebral cortex: analyses and implications. J Neuroimmunol 25:63–74
Sminia T, DeGroot CJA, Dijkstra CD, Koetsier JC, Polman CH (1987) Macrophages in the central nervous system of the rat. Immunobiology 174:43–50
Streit WJ, Graeber MB, Kreutzberg GW (1988) Functional plasticity of microglia: a review. GLIA 1:301–307
Suzuki H, Franz H, Yamamoto T, Iwasaki Y, Konno H (1988) Identification of the normal microglial population in human and rodent nervous tissue using lectin-histochemistry. Neuropathol Appl Neurobiol 14:221–227
Szumanska G, Vorbrodt AW, Mandybur TI, Wisniewski HM (1987) Lectin histochemistry of plaques and tangles in Alzheimer's disease. Acta Neuropathol (Berl) 73:1–11
Unanue ER, Allen PM (1986) Comment on the finding of Ia expression in nonlymphoid cells. Lab Invest 55:123–125
Vazeux R, Brousse N, Jarry A, Henin D, Marche C, Vedrenne C, Mikol J, Wolff M, Michon C, Rozenbaum W, Bureau J-F, Montagnier L, Brahic M (1987) AIDS subacute encephalitis: identification of HIV-infected cells. Am J Pathol 126:403–410
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sasaki, A., Nakanishi, Y., Nakazato, Y. et al. Application of lectin and B-lymphocyte-specific monoclonal antibodies for the demonstration of human microglia in formalin-fixed, paraffin-embedded brain tissue. Vichows Archiv A Pathol Anat 419, 291–299 (1991). https://doi.org/10.1007/BF01606520
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01606520