CALCIUM DEPENDENCE OF GLUCOCORTICOID-INDUCED LYMPHOCYTOLYSIS

CALCIUM DEPENDENCE OF GLUCOCORTICOID-INDUCED LYMPHOCYTOLYSIS
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DOI:
10.1073/pnas.74.2.638
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发表时间:
1977-01-01
影响因子:
11.1
通讯作者:
EDELMAN, IS
EDELMAN, IS
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KAISER, N;EDELMAN, IS

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一种强效糖皮质激素,曲安奈德(9 α-氟-11 β,16. α,17. α,21-四羟基孕甾-1,4-二烯-3,20-二酮-16,17-丙酮化合物)和二价阳离子离子载体(A23187 [2-[3 β,9. α,11. β-三甲基)-8-(2-吡咯羧甲基)-1,7-二氧杂螺[6.6]十一烷基-2 β-甲基]-5-甲基氨基苯并恶唑-4-羧酸])在体外对肾上腺切除大鼠胸腺细胞的[3 H]尿苷摄取和溶解具有相似的作用。从培养基中去除Ca 2+减弱了曲安奈德的溶细胞作用,并几乎消除了A23187的溶细胞作用。在无钙培养基中,用曲安奈德或A23187处理胸腺细胞15小时,然后重新引入钙离子迅速降低细胞存活率。根据反应的时间过程,曲安奈德和A23187诱发成比例增加45 Ca摄取和溶解的胸腺细胞。这些发现暗示糖皮质激素依赖性淋巴细胞溶解中的Ca 2+摄取增强。
A potent glucocorticoid, triamcinolone acetonide (9.alpha.-fluoro-11.beta.,16.alpha.,17.alpha.,21-tetrahydroxypregna-1,4-diene-3,20-dione-16,17-acetonide) 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]) had similar effects in vitro on [3H]uridine uptake and on lysis of thymocytes of adrenalectomized rats. Removal of Ca2+ from the medium blunted the cytolytic action of triamcinolone acetonide and virtually eliminated that of A23187. In Ca2+-free media, treatment of the thymocytes for 15 h with triamcinolone acetonide or A23187 followed by re-introduction of Ca2+ rapidly decreased cell survival. Based on the time courses of the responses, triamcinolone acetonide and A23187 evoked proportionate increases in 45Ca uptake and lysis of the thymocytes. These findings implicate enhanced Ca2+ uptake in glucocorticoid-dependent lymphocytolysis.