有机锡诱导胸腺萎缩的细胞和分子层面

Cellular and molecular aspects of organotin-induced thymus atrophy.

作者信息

Pieters R H, Bol M, Seinen W, Penninks A H

机构信息

Research Institute of Toxicology, Utrecht University, The Netherlands.

出版信息

Hum Exp Toxicol. 1994 Dec;13(12):876-9. doi: 10.1177/096032719401301210.

DOI:10.1177/096032719401301210

Abstract

Organotin compounds, di-n-butyltin dichloride (DBTC) in particular, have been shown to cause thymus atrophy in the rat. 2. DBTC-induced thymus atrophy results from a depletion of small CD4+CD8+ thymocytes which is caused by a diminished production of immature CD4-CD8+ and CD4+CD8+ thymoblasts. 3. DBTC inhibits the activation, but not the differentiation of immature CD4-CD8+ thymocytes in vitro and in vivo suggesting a selective antiproliferative activity of DBTC. 4. DBTC inhibits the adhesion molecule-mediated binding of thymocytes to thymic epithelial cells. 5. DBTC enhances the Ca2+ release elicited by cross-linking of the T cell receptor complex (TcR alpha beta-CD3) on thymocytes and moreover delays cap formation of the TcR alpha beta-CD3 receptor. 6. It is concluded that DBTC possibly interferes with the functioning of the cytoskeleton. The relation of the in vitro findings to the inhibition of immature CD4-CD8+ thymocyte activation and the induction of thymus atrophy is unknown as yet.

摘要

有机锡化合物，尤其是二正丁基二氯化锡（DBTC），已被证明可导致大鼠胸腺萎缩。2. DBTC诱导的胸腺萎缩是由于小CD4+CD8+胸腺细胞耗竭所致，这是由未成熟CD4-CD8+和CD4+CD8+胸腺母细胞生成减少引起的。3. DBTC在体外和体内均抑制未成熟CD4-CD8+胸腺细胞的活化，但不抑制其分化，提示DBTC具有选择性抗增殖活性。4. DBTC抑制粘附分子介导的胸腺细胞与胸腺上皮细胞的结合。5. DBTC增强胸腺细胞上T细胞受体复合物（TcRαβ-CD3）交联引发的Ca2+释放，而且延迟TcRαβ-CD3受体的帽形成。6. 得出的结论是，DBTC可能干扰细胞骨架的功能。体外研究结果与未成熟CD4-CD8+胸腺细胞活化抑制及胸腺萎缩诱导之间的关系尚不清楚。