Abstract
Lysosomal proteinases are increased in the tissue lesions of experimental allergic encephalomyelitis and have been implicated in the degradation of myelin proteins. The cellular origins of the increased proteinases are not known but reactive astrocytes found in areas of increased activity are candidate cells. To evaluate the potential of astrocytes as the source of these proteinases, cathepsin B (CB) and cathepsin D (CD) levels were measured in lysates of cultured astrocytes from neonatal rats. Because astrocytes are activated by inflammatory mediators in demyelinating lesions the effect of activation on proteinase levels was examined. Culture supernatants from mononuclear leukocytes stimulated with either concanavalin A or phytohemagglutinin (PHA) induced significant increases in the astrocytic proteinases. Neither PHA alone, interleukin-1, interleukin-2, nor gamma-interferon induced significant increases. Fractions of the supernatant from PHA stimulated mononuclear leukocytes were tested and activity was found in fractions corresponding to a molecular weight of 45–50,000. These studies demonstrate that astrocytes contain significant amounts of CB and CD activity which can be increased by a factor or factors released by activated mononuclear leukocytes.
Similar content being viewed by others
References
Rauch, H. C., Einstein, E. R., and Csejtey, J. 1973. Enzymatic degradation of myelin basic protein in central nervous system lesions of monkeys with experimental allergic encephalomyelitis. Neurobiology 3:195–205.
Smith, M. E., Sedgewick, L. M., and Tagg, J. S. 1974. Proteolytic enzymes and experimental demyelination in the rat and monkey. J. Neurochem. 23:965–971.
Hirsch, H. E., and Parks, M. E. 1975. Acid proteinases and other acid hydrolases in experimental allergic encephalomyelitis. Neurobiology 3:195–205.
Bowen, D. M., and Davison, A. N. 1973. Cathepsin A in human brain and spleen. Biochem. J. 131:417–419.
Merrill, J. E., Kutsunia, S., Mohlstrom, C., Hofman, F., Groppman, J., and Golde, D. W. 1984. Proliferation of astroglia, and oligodendroglia in response to human T cell derived factors. Science 224:1428–1430.
Fontana, A., Fierz, W., and Wekerle, H. 1984. Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature 307:273–276.
Eng, L. F., Smith, M. E., and Gerstl, B. 1986. Glial contribution to experimental allergic encephalomyelitis. Pages 381–388in Grisar, T., Franck, G., Hertz, L., Norton, M., Sensenbrauer, M., and Woodbury, D. (eds.). Dynamic properties of glial cells. Cellular and molecular aspects. Pergamon Press, (Oxford, England).
Smith, M. E., Somera, F. P., and Eng, L. G. 1983. Immunocytochemical staining for glial fibrillary acidic protein and the metabolism of cytoskeletal proteins in experimental allergic encephalomyelitis. Brain Res. 264:241–253.
Massacesi, L., Abbamondi, A. L., Raimondi, L., Giorgi, C., and Amaducci, L. 1988. Lysosomal enzymes in experimental allergic encephalomyelitis: time course and evidence of the source. Neurochem. Res. 13:165–169.
McCarthy, K. and DeVellis, J. 1980. Oligodendroglia and astroglial cell cultures. J. Cell. Biol. 85:890–902.
Barrett, A. J. and Kirschke, H. 1981. Cathepsin B, Cathepsin H, and cathepsin L. Methods of Enzymol. 80:535–561.
Whitaker, J. N. and Seyer, J. M. 1979. The sequential limited degradation of bovine myelin basic protein by bovine brain cathepsin D. J. Biol. Chem. 254:6959–6963.
Hirsch, M. R., Wietzerbin, J., Pierres, M., and Goridis, C. 1983. Expression of Ia antigens by cultured astrocytes treated with gamma-interferon. Neurosci. Lett. 41:199–204.
Wong, G. H., Bartlett, P. F., Clark-Lewis, I., Battye, F., and Schrader, J. W. 1984. Inducible expression of H-2 and Ia antigens on brain cells. Nature 310:688–691.
Giulian, D. and Lachman, L. B. 1985. Interleukin-1 stimulation of astroglial proliferation after brain injury. Science 228:497–499.
Pulver, M., Carrel, S., Mach, J. P., de Tribolet, N. 1987. Cultured human fetal astrocytes can be induced by interferon-gamma to express HLA-DR. J. Neuroimmunol. 14:123–133.
Snyder, D. S., Simonis, S., Uzman, B. G., and Whitaker, J. N. 1985. Rat neural tissue cathepsin D. J. Neurocytology 14:579–596.
Toshinawal, P., Tiku, K., Skosey, J. L., Tiku, M. L., 1984. Modulation of cerebral cell plasminogen activator activity. Neurol 34 [suppl 1]:196.
Toshinawal, P., Firestone, S., Barlow, G., Tiku, M. L., 1985. Astrocyte plasminogen activator is tissue type. Neurol 35 [suppl 1]:269.
Toshinawal, P., Tiku, K., Skosey, J. L., Tiku, M. L., 1985. Lymphokines enhance astrocyte plasminogen activator activity. Neurol 35 [suppl 1]:269.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bever, C.T., Snyder, D.S., Endres, R.O. et al. Activation of astrocytic lysosomal proteinases by factors released by mononuclear leukocytes. Neurochem Res 14, 37–41 (1989). https://doi.org/10.1007/BF00969755
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00969755