Jirasakuldech B, Schussler G C, Yap M G, Drew H, Josephson A, Michl J
Department of Medicine, State University of New York Health Sciences Center, Brooklyn 11203, USA.
J Clin Endocrinol Metab. 2000 Nov;85(11):3996-9. doi: 10.1210/jcem.85.11.6966.
T4-binding globulin (TBG), the principal thyroid hormone-binding protein of serum, is a member of the serine protease inhibitor (serpin) superfamily. We report a characteristic serpin cleavage product of TBG in sepsis sera. At 49-50 kDa, the TBG remnant is 4-5 kDa smaller than the intact protein and is the same molecular mass as a TBG cleavage product produced by incubation with polymorphonuclear elastase. Incubation with polymorphonuclear leukocytes also produces the 49- to 50-kDa remnant, and this proteolysis is stimulated by zymosan activation. Polymorphonuclear cell cleavage of TBG increases the ratio of free/bound T4. As previously described, in vitro cleavage of TBG by elastase also increases free/bound T4. These findings are consistent with the hypothesis that serine proteases present at inflammatory sites cleave TBG, releasing its hormonal ligands.
甲状腺素结合球蛋白（TBG）是血清中主要的甲状腺激素结合蛋白，属于丝氨酸蛋白酶抑制剂（serpin）超家族。我们报告了脓毒症血清中一种具有特征性的TBG丝氨酸蛋白酶抑制剂裂解产物。TBG残余物分子量为49 - 50 kDa，比完整蛋白小4 - 5 kDa，与经多形核弹性蛋白酶孵育产生的TBG裂解产物分子量相同。与多形核白细胞孵育也会产生49至50 kDa的残余物，这种蛋白水解作用受酵母聚糖激活的刺激。多形核细胞对TBG的裂解会增加游离/结合型T4的比例。如先前所述，弹性蛋白酶在体外对TBG的裂解也会增加游离/结合型T4的比例。这些发现与以下假设一致：炎症部位存在的丝氨酸蛋白酶会裂解TBG，释放其激素配体。
