AGE-RELATED AND DEXAMETHASONE-INDUCED CHANGES IN CATHEPSIN-E AND CATHEPSIN-D IN RAT THYMIC AND SPLENIC CELLS

Age-related and dexamethasone (DEX)-induced changes in the cellular le vels, distributions, and molecular forms of two distinct intracellular aspartic proteinases, cathepsin E (CE) and cathepsin D (CD), were inv estigated in rat thymus and spleen by immunohistochemical and quantita tive analyses. In the thymus, CE was predominantly restricted to thymo cytes and macrophage-like cells, whereas CD was associated mainly with the stromal cells. The increased thymic CE level observed in young ra ts up to 8 weeks of age was markedly decreased in aged rats (78-80 wee ks of age), in accordance with the involution of the thymus, while the re was little difference in the thymic CD level between young and aged rats. Subcutaneous administration of DEX also caused a marked decreas e of the thymic CE level in response to the depletion of thymocytes. I n contrast, a great accumulation of CD occurred in the thymic stromal cells after DEX treatment. Immunoblotting analyses revealed that CE in thymocytes isolated from young rats consisted predominantly of a 46-k Da preform which was greatly converted into a 42-kDa mature form in DE X-treated thymocytes. This conversion, however, was scarcely observed during the normal aging process. In the spleen, CE was also abundant i n macrophage-like cells and lymphocytes and its level was not signific antly changed between young and aged rats. However, DEX treatment caus ed a marked decrease of the splenic CE and CD levels in accordance wit h the depletion of the white pulp. Among the lymphoid cell types exami ned, splenic B cells were the most abundant in CE. The CE level in thy mocytes and splenic T-cells was more than twice that in circulating ly mphocytes. We concluded that CE is related to the process of activatio n-induced lymphocyte depletion. (C) 1996 Academic Press, Inc.