Brix K, Herzog V
Institut für Zellbiologie, Rheinische Friedrich-Wilhelms Universität, Bonn, Germany.
J Clin Invest. 1994 Apr;93(4):1388-96. doi: 10.1172/JCI117115.
Thyroglobulin appears in the circulation of vertebrates at species-specific concentrations. We have observed that the clearance of thyroglobulin from the circulation occurs in the liver by macrophages. Here we show that the thyroid hormones T3 and T4 were released by incubation of mouse macrophages (J774) with thyroglobulin. Thyroid hormone release was a fast process, with an initial rate of approximately 20 pmol T4/mg per min and approximately 0.6 pmol T3/mg per min, indicating that macrophages preferentially release T4. The bulk of released thyroid hormones appeared after 5 min of incubation of macrophages with thyroglobulin, whereas degradation of the protein was detectable only after several hours. During internalization of thyroglobulin, endocytic vesicles and endosomes were reached at 5 min and lysosomes at 60 min. T4 release started extracellularly by secreted proteases and continued along the endocytic pathway of thyroglobulin, whereas T3 release occurred mainly intracellularly when thyroglobulin had reached the lysosomes. This shows that the release of both hormones occurred at distinct cellular sites. Our in vitro observations suggest that macrophages in situ represent an extrathyroidal source for thyroid hormones from circulating thyroglobulin.
甲状腺球蛋白以物种特异性浓度出现在脊椎动物的循环系统中。我们观察到，甲状腺球蛋白从循环系统中的清除是由肝脏中的巨噬细胞完成的。在此我们表明，小鼠巨噬细胞（J774）与甲状腺球蛋白一起孵育时会释放甲状腺激素T3和T4。甲状腺激素的释放是一个快速过程，初始速率约为每分钟20皮摩尔T4/毫克和约0.6皮摩尔T3/毫克，这表明巨噬细胞优先释放T4。巨噬细胞与甲状腺球蛋白孵育5分钟后，大部分释放的甲状腺激素出现，而蛋白质的降解在数小时后才检测到。在甲状腺球蛋白内化过程中，5分钟时到达内吞小泡和内体，60分钟时到达溶酶体。T4通过分泌的蛋白酶在细胞外开始释放，并沿着甲状腺球蛋白的内吞途径持续释放，而T3的释放主要发生在甲状腺球蛋白到达溶酶体时的细胞内。这表明两种激素的释放发生在不同的细胞部位。我们的体外观察结果表明，原位巨噬细胞是循环甲状腺球蛋白产生甲状腺激素的甲状腺外来源。
