Age-Related and Dexamethasone-Induced Changes in Cathepsins E and D in Rat Thymic and Splenic Cells

Abstract

Age-related and dexamethasone (DEX)-induced changes in the cellular levels, distributions, and molecular forms of two distinct intracellular aspartic proteinases, cathepsin E (CE) and cathepsin D (CD), were investigated in rat thymus and spleen by immunohistochemical and quantitative analyses. In the thymus, CE was predominantly restricted to thymocytes and macrophage-like cells, whereas CD was associated mainly with the stromal cells. The increased thymic CE level observed in young rats up to 8 weeks of age was markedly decreased in aged rats (78–80 weeks of age), in accordance with the involution of the thymus, while there was little difference in the thymic CD level between young and aged rats. Subcutaneous administration of DEX also caused a marked decrease of the thymic CE level in response to the depletion of thymocytes. In 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-kDa proform which was greatly converted into a 42-kDa mature form in DEX-treated thymocytes. This conversion, however, was scarcely observed during the normal aging process. In the spleen, CE was also abundant in macrophage-like cells and lymphocytes and its level was not significantly changed between young and aged rats. However, DEX treatment caused a marked decrease of the splenic CE and CD levels in accordance with the depletion of the white pulp. Among the lymphoid cell types examined, splenic B cells were the most abundant in CE. The CE level in thymocytes and splenic T-cells was more than twice that in circulating lymphocytes. We concluded that CE is related to the process of activation-induced lymphocyte depletion.