Skip to main content
Log in

Ultrastructural cytochemical demonstration of peroxidase-positive monocyte granules: An additional method for studying the origin of mononuclear cells in encephalitic lesions

  • Original Investigations
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Unlike lymphocytes, blood monocytes possess in their cytoplasm peroxidase-positive (azurophil) granules (ppg) which largely correspond to the homonymous organelles of neutrophil granulocytes. We tested whether ppg, demonstrated cytochemically at the submicroscopic level, could serve as markers of monocyte-derived reactive mononuclear cells in encephalitic lesions. Samples of cerebrocortical tissue from adult albino mice with experimental yellow fever virus encephalitis were incubated in a medium containing diaminobenzidine and H2O2 for localization of peroxidatic activity. Mononuclear cells exhibiting ppg were found (1) in the lumen of brain venules, (2) in different stages of migration through the walls of such vessels, (3) in perivascular areas, (4) in the glioneuropil, either loosely scattered or forming small clusters, (5) in a satellite position to neurons, and (6) in leptomeningitic infiltrates. Several mononuclear elements harboring ppg had assumed an elongated, rod cell-like out-line. Amongst the peroxidase-negative mononuclears were fully developed brain macrophages and elements showing morphologic features characteristic of activated lymphocytes. Most mononuclear cells without ppg resembled the peroxidase-reactive ones. The results of this study provide direct evidence in favor of a monocytic origin of, at least, numerous reactive mononuclear elements in encephalitic lesions. The approach followed in the present study is not suitable for quantitative investigations of the histogenesis of mononuclear cells responding to brain injuries, since emigrated blood monocytes rapidly lose their ppg, particularly, when they display enhanced phagocytic activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Anzil, A. P., Blinzinger, K.: Electron microscopic studies of rabbit central and peripheral nervous system in experimental Borna disease. Acta neuropath. (Berl.)22, 305–318 (1972)

    Google Scholar 

  • Bainton, D. F., Farquhar, M. G.: Segregation and packaging of granule enzymes in eosinophilic leukocytes. J. Cell Biol.45, 54–73 (1970)

    Google Scholar 

  • Bentfeld, M. E., Nichols, B. A., Bainton, D. F.: Ultrastructural localization of peroxidase in leukocytes of rat bone marrow and blood. Anat. Rec.187, 219–240 (1977)

    Google Scholar 

  • Blinzinger, K.: Comparative electron microscopic studies of several experimental group B arbovirus infections of the murine CNS (CEE virus, Zimmern virus, yellow fever virus). Ann. Inst. Pasteur123, 497–519 (1972)

    Google Scholar 

  • Blinzinger, K.: Vergleichende elektronenmikroskopische Untersuchungen bei experimentellen Infektionen mit dem fränkischen Zimmern-Virus (Stamm ZIU VIII-BM) und zwei bekannten Togaviren der Gruppe B. In: Arboviruserkrankungen des Nervensystems in Europa, S. 124–143 (W. K. Müller und G. Schaltenbrand, Hrsg.). Stuttgart: Thieme 1975

    Google Scholar 

  • Blinzinger, K., Luh, S., Anzil, A. P.: Die neuronalen Torres-Körperchen bei der experimentellen Gelbfieber-Encephalomyelitis. Ein weiteres Beispiel für die uneinheitliche Natur der Kerneinschlüsse vom Typ A nach Cowdry. Arch. Psychiat. Nervenkr.221, 199–212 (1976)

    Google Scholar 

  • Daems, W. T., Wisse, E., Brederoo, P., Emeis, J. J.: Peroxidatic activity in monocytes and macrophages. In: Mononuclear phagocytes in immunity, infection, and pathology, pp. 57–77 (R. van Furth, Ed.). Oxford: Blackwell 1975

    Google Scholar 

  • Fujita, S., Kitamura, T.: Origin of brain macrophages and the nature of microglia. In: Progress in neuropathology, Vol. III, pp. 1–50 (H. M. Zimmerman, Ed.). New York: Grune and Stratton 1976

    Google Scholar 

  • Graham, R. C., Karnovsky M. J.: The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney. Ultrastructural cytochemistry by a new technique. J. Histochem. Cytochem.14, 291–302 (1966)

    Google Scholar 

  • Herzog, V., Miller, F. Die Lokalisation endogener Peroxydase in der Glandula parotis der Ratte. Z. Zellforsch.107, 403–420 (1970)

    Google Scholar 

  • Imamoto, K., Leblond, C. P.: Presence of labeled monocytes. macrophages and microglia in a stab wound of the brain following an injection of bone marrow cells labeled with3H-uridine into rats. J. comp. Neurol.174, 255–279 (1977)

    Google Scholar 

  • Johnson, R. T.: Inflammatory response to viral infection. Res. Publ. Ass. Res. nerv. ment. Dis.49, 305–310 (1971)

    Google Scholar 

  • Karnovsky, M. J.: A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J. Cell Biol.27, 137A-138A (1965)

    Google Scholar 

  • Kitamura, T.: Hematogenous cells in experimental Japanese encephalitis. Acta neuropath. (Berl.)32, 341–346 (1975)

    Google Scholar 

  • Kitamura, T., Fujita, S.: Cells of the reticulcendothelial system in the brain and their relationship to circulating leukocytes, microglia and pericytes. Rec. Adv. RES Res.13, 48–60 (1973)

    Google Scholar 

  • Kitamura, T., Hattori, H., Fujita, S.: EM-autoradiographic studies on the inflammatory cells in the experimental Japanese encephalitis (in Japanese with English summary). J. Electr. Microsc. (Tokyo)21, 315–322 (1972)

    Google Scholar 

  • Miller, F., Herzog, V. Die Lokalisation von Peroxydase und saurer Phosphatase in eosinophilen Leukocyten während der Reifung. Elektronenmikroskopisch-cytochemische Untersuchungen am Knochenmark von Ratte und Kaninchen. Z. Zellforsch.97, 84–110 (1969)

    Google Scholar 

  • Nichols, B. A., Bainton, D. F.: Ultrastructure and cytochemistry of mononuclear phagocytes. In: Mononuclear phagocytes in immunity, infection, and pathology, pp. 17–55 (R. van Furth, Ed.). Oxford: Blackwell 1975

    Google Scholar 

  • Oehmichen, M.: Mohocytic origin of microglia cells. In: Mononuclear phagocytes in immunity, infection, and pathology, pp. 223–240 (R. van Furth, Ed.). Oxford: Blackwell 1975

    Google Scholar 

  • Oehmichen, M.: Mononukleäre Phagozyten im Zentralnervensystem. Herkunft, Verteilungsmodus, Funktion. Habilitationsschrift, Univ. Tübingen 1977

  • Oehmichen, M., Genčić, M.: Experimental studies on kinetics and functions of mononuclear phagozytes of the central nervous system. Acta neuropath. (Berl.) Suppl.VI, 285–290 (1975)

    Google Scholar 

  • Oehmichen, M., Grüninger, H., Saebisch, R., Narita, Y.: Mikroglia und Pericyten als Transformationsformen der Blut-Monocyten mit erhaltener Proliferationsfähigkeit. Experimentelle autoradiographische und enzymhistochemische Untersuchungen am normalen und geschädigten Kaninchen- und Rattengehirn. Acta neuropath. (Berl.)23, 200–218 (1973)

    Google Scholar 

  • Palade G. E.: A study of fixation for electron microscopy. J. exp. Med.95, 285–298 (1952)

    Google Scholar 

  • Rosenstreich, D. I., Shevach, E., Green, I., Rosenthal, A. S.: The uropod-bearing lymphocyte of the guinea pig. Evidence for thymic origin. J. exp. Med.135, 1037–1048 (1972)

    Google Scholar 

  • Sato, M.:3H-thymidine autoradiographic studies on the origin of reactive cells in the brain of mice infected with Japanese encephalitis virus (in Japanese with English Abstract). Brain and Nerve (Tokyo)20, 1239–1250 (1968)

    Google Scholar 

  • Smith, E. R., Farquhar, M. G.: Preparation of non-frozen sections for electron microscope cytochemistry. Sci. Instr. News (RCA)10, 13–18 (1965)

    Google Scholar 

  • Van der Rhee, H. J., de Winter C. P. M., Daems, W. T.: Fine structure and peroxidatic activity of rat blood monocytes. Cell Tiss. Res.185, 1–16 (1977)

    Google Scholar 

  • Wong-Riley, M. T. T.: Endogenous peroxidatic activity in brain stem neurons as demonstrated by their staining with diaminobenzidine in normal squirrel monkeys. Brain Res.108, 257–277 (1976)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported in part by a research fellowship awarded to Dr. Heike Herrlinger by the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, Federal Republic of Germany

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blinzinger, K., Herrlinger, H., Luh, S. et al. Ultrastructural cytochemical demonstration of peroxidase-positive monocyte granules: An additional method for studying the origin of mononuclear cells in encephalitic lesions. Acta Neuropathol 43, 55–61 (1978). https://doi.org/10.1007/BF00684998

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00684998

Key words

Navigation