Activation of astrocytic lysosomal proteinases by factors released by mononuclear leukocytes

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.