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Ki-M1P as a marker for microglia and brain macrophages in routinely processed human tissues

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Summary

The monoclonal antibody Ki-M1P recognizes a formalin/paraffin-resistant differentiation epitope of monocytes and their macrophage derivatives [Radzun et al., Lab Invest 65:306, 1991]. To evaluate its usefulness for neuropathology, we examined a variety of routinely processed tissues using immunohistochemistry. In normal brains, positivity was restricted to ramified microglial cells. Intense labeling of macrophages, ramified and ameboid microglial cells, and rod cells was seen in brains with various degenerative and inflammatory disorders. Astrocytes were negative as determined by double-immunofluorescence labeling using Ki-M1P and anti-glial fibrillary acidic protein (GFAP). Histiocytic lesions (histiocytosis X, xanthogranulomas, granulomatous inflammation) were immunopositive. Among 107 tumors, reactivity of Ki-M1P was observed with some schwannoma and meningioma tumor cells. In addition to macrophages, most gliomas contained small, elongated Ki-M1P-positive cells, which were negative for GFAP. Positivity was also found in two glioblastoma cell lines. Immunoblotting performed on spleen, meningioma and glioblastoma specimens revealed one to three bands in the range of 110 to 130 kDa. We conclude that Ki-M1P can serve as a reliable marker for brain macrophages and microglial cells in routinely processed normal and non-neoplastic tissues, whereas due to the unexpected immunoreactivities results obtained with neoplastic tissues should be carefully interpreted.

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References

  1. Chou SM, Miles JM (1989) B-cell immunomarkers recognize rod cells in paraffin sections (abstract). J Neuropathol Exp Neurol 48:344

    Google Scholar 

  2. Cras P, Gheuens J, Lübke U, Boons J, Vandermeeren M, Van Heuverswijn H, Martin JJ (1990) A monoclonal antibody raised against Alzheimer cortex that specifically recognizes a subpopulation of microglial cells. J Histochem Cytochem 38:1201–1207

    Google Scholar 

  3. Dickson DW, Mattiace LA (1989) Astrocytes and microglia in human brain share an epitope recognized by a B-lymphocyte-specific monoclonal antibody (LN-1). Am J Pathol 135:135–147

    Google Scholar 

  4. Dickson DW, Mattiace LA, Kure K, Hutchins K, Lyman WD, Brosnan CF (1991) Microglia in human disease, with an emphasis on acquired immune deficiency syndrome. Lab Invest 64:135–156

    Google Scholar 

  5. Dolman CL (1991) Microglia. In: Davis RL, Robertson DM (eds) Textbook of neuropathology, 2nd edn. Williams & Wilkins, Baltimore, pp 141–174

    Google Scholar 

  6. Esiri MM, McGee JO'D (1986) Monoclonal antibody to macrophages (EMB/11) labels macrophages and microglial cells in human brain. J Clin Pathol 39:615–621

    Google Scholar 

  7. Esiri MM, Morris CS (1991) Immunocytochemical study of macrophages and microglial cells and extracellular matrix components in human CNS disease. 2. Non-neoplastic diseases. J Neurol Sci 101:59–72

    Google Scholar 

  8. Graeber MB, Streit WJ (1990) Microglia: immune network in the CNS. Brain Pathol 1:2–5

    Google Scholar 

  9. 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

    Google Scholar 

  10. Greywoode GIN, McCarthy SP, McGee JO'D (1990) Labelling of cells of the mononuclear phagocyte system in routinely processed archival biopsy specimens with monoclonal antibody EBM/11. J Clin Pathol 43:992–996

    Google Scholar 

  11. 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 77:569–575

    Google Scholar 

  12. Hulette CM, Downey BT, Burger PC (1992) Macrophage markers in diagnostic neuropathology. Am J Surg Pathol 16:493–499

    Google Scholar 

  13. Jellinger K, Paulus W, Grundke-Iqbal I, Riederer P, Youdim MBH (1990) Brain iron and ferritin in Parkinson's and Alzheimer's diseases. J Neural Transm [P-D Sect] 2:327–340

    Google Scholar 

  14. Kaneko Y, Kitamoto T, Tateishi J, Yamaguchi K (1989) Ferritin immunohistochemistry as a marker for microglia. Acta Neuropathol 79:129–136

    Google Scholar 

  15. Kusaka H, Hirano A, Bornstein MB, Moore GRW, Raine CS (1986) Transformation of cells of astrocyte lineage into macrophage-like cells in organotypic cultures of mouse spinal cord tissue. J Neurol Sci 72:77–89

    Google Scholar 

  16. Mannoji H, Yeger H, Becker LE (1986) A specific histochemical marker (lectin Ricinus communis agglutinin-1) for normal human microglia, and application to routine histopathology. Acta Neuropathol (Berl) 71:341–343

    Google Scholar 

  17. McKeever PE, Davenport RD, Shakui P (1991) Patterns of antigenic expression of human glioma cells. Crit Rev Neurobiol 6:119–147

    Google Scholar 

  18. Miles JM, Chou SM (1988) A new immunoperoxidase marker for microglia in paraffin sections. J Neuropathol Exp Neurol 47:579–587

    Google Scholar 

  19. Morimura T, Neuchrist C, Kitz K, Budka H, Scheiner O, Kraft D, Lassmann H (1990) Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation. Acta Neuropathol 80:287–294

    Google Scholar 

  20. Morris CS, Esiri MM (1991) Immunocytochemical study of macrophages and microglial cells and extracellular matrix components in human CNS diseases. 1. Gliomas. J Neurol Sci 101:47–58

    Google Scholar 

  21. Paulus W, Kirchner T, Ott MM, Kühl J, Warmuth-Metz M, Sörensen N, Müller-Hermelink HK, Roggendorf W (1992) Histiocytic tumor of Meckel's cave. An intracranial equivalent of juvenile xanthogranuloma of the skin. Am J Surg Pathol 16:76–83

    Google Scholar 

  22. Radzum HJ, Hansmann ML, Heidebrecht HJ, Bödewadt-Radzun S, Wacker HH, Kreipe H, Lumbeck H, Hernandez C, Kuhn C, Parwaresch MR (1991) Detection of a monocyte/macrophage differentiation antigen in routinely processed paraffin-embedded tissues by monoclonal antibody Ki-M1P. Lab Invest 65:306–315

    Google Scholar 

  23. Rossi ML, Hughes JT, Esiri MM, Coakham HB, Brownell DB (1987) Immunohistological study of mononuclear cell infiltrate in malignant gliomas. Acta Neuropathol (Berl) 74:269–277

    Google Scholar 

  24. Sasaki A, Nakanishi Y, Nakazato Y, Yamaguchi H (1991) Application of lectin and B-lymphocyte-specific monoclonal antibodies for the demonstration of human microglia in formalin-fixed, paraffin-embedded brain tissue. Virchows Arch [A] 419:291–299

    Google Scholar 

  25. Shuangshoti S, Samranvej P, Netsky MG (1979) Phagocytic astrocytes and neurons in old encephalomalacia. J Neuropathol Exp Neurol 38:235–241

    Google Scholar 

  26. Stockinger H (1989) Cluster report: CD68. In: Knapp W (ed) Leukocyte typing IV. White cell differentiation antigens. Oxford University Press, Oxford, pp 841–843

    Google Scholar 

  27. Sung JH, Manivel JC, Nakhleh RE, Wick MR (1988) Microglia/macrophages (Mi/Ma) of human brains: an immunohistochemical study (abstract). J Neuropathol Exp Neurol 47:385

    Google Scholar 

  28. Watabe K, Osborne D, Kim SU (1989) Phagocytic activity of human adult astrocytes and oligodendrocytes in culture. J Neuropathol Exp Neurol 48:499–506

    Google Scholar 

  29. Zucker-Franklin D, Warfel A, Grusky G, Frangione B, Teitel D (1987) Novel monocyte-like properties of microglia/astroglial cells. Lab Invest 57:176–185

    Google Scholar 

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Dedicated to Professor Jürgen Peiffer on occasion of his 70th birthday

Supported by the Wilhelm Sander Foundation

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Paulus, W., Roggendorf, W. & Kirchuer, T. Ki-M1P as a marker for microglia and brain macrophages in routinely processed human tissues. Acta Neuropathol 84, 538–544 (1992). https://doi.org/10.1007/BF00304473

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  • DOI: https://doi.org/10.1007/BF00304473

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