Further Studies on the Role of Calcium in Glucocorticoid-Induced Lymphocytolysis*

Publisher Website
Google Scholar
Abstract
In a previous study comparing the effects of triamcinolone acetonide (TA) and a divalent cation ionophore A23187, [2-[(3.beta.,9.alpha., 11.beta.-trimethyl)-8-(2-pyrrolecarboxymethyl)-1,7-dioxaspiro[6-6]undecyl-2.beta.-methyl]-5-methylaminobenzoxazole-4-carboxylic acid] on rat thymocytes, an important contributory role for Ca2+ in glucocorticoid-induced cytolysis was proposed. The plausibility of this hypothesis was tested further in thymic lymphocytes (thymocytes) and lymph node lymphocytes (LN-lymphocytes). Thymocytes incubated in a Ca2+-containing medium responded to TA or A23187 with a concentration-dependent decrease in the number of viable cells. TA-induced cytolysis was reduced in Ca-free medium and was equally supported by Ca2+ and Sr2+, but not by Ba2+. A23187-induced cytolysis was supported by Ca2+ > Sr2+, but not by Ba2+. Thymocytes were also lysed by increasing concentrations of Ca2+ even in the absence of TA and A23187. LN-Lymphocytes, however, were less sensitive to the cytotoxic effects of Ca2+ under the same conditions. In the presence of Ca2+, thymocytes were lysed to a greater extent than LN-lymphocytes by TA, whereas the sensitivities to A23187-induced cytolysis were the same in both populations. Omission of Ca2+ from the incubation medium inhibited the cytolytic response to TA only in thymocytes. A23187-induced cytolysis was impaired in Ca-free medium in both thymocytes and LN-lymphocytes. These observations apparently confirm the previous findings on Ca2+ dependence of glucocorticoid-induced cytolysis in thymocytes. This pathway, however, may not be involved in glucocorticoid-induced cytolysis of LN-lymphocytes. Thus, a more basic and as yet undefined mechanism probably mediates the lymphocytolytic process.