Kaczmarek E, Liu Y, Berse B, Chen C S, McDonagh J
Department of Pathology, Beth Israel Hospital, Boston, MA.
Biochim Biophys Acta. 1995 Feb 22;1247(1):127-34. doi: 10.1016/0167-4838(94)00167-f.
Factor XIIIa belongs to a family of ubiquitous transglutaminases, which catalyze formation of covalent bonds between the epsilon-amino group of specific lysines and the gamma-carboxyl group of glutamines. Factor XIII is synthesized as a zymogen and after activation, it participates in both the coagulation and fibrinolytic mechanisms. Most transglutaminases are intracellular, but factor XIII is both intracellular and extracellular. the biosynthesis of extracellular (plasma) factor XIII, with the structure of a noncovalent heterotetramer, A2B2, is complex. Here, evidence is presented from PCR analysis and Northern blotting that mRNAs for both A and B subunits are present in the liver. The distribution of mRNA, specific for factor XIII subunits, in various human tissues was also analyzed. Among the tissues examined, the only signal for B subunit was found in the liver. For subunit A, the signal was observed in placenta, liver, kidney, lung, skeletal muscle and heart with varying intensities; in brain or pancreas there was no signal. With an immunoperoxidase method, factor XIII A subunit was identified in the PLC/PRF/5 cell line. By ELISA and reverse immunoblotting, with antibodies specific for the A-B complex, it was also shown that these cells produce and secrete factor XIII. From all of these results, we conclude that the liver is a source of plasma factor XIII, and that the complex A2B2 is secreted from these cells.
凝血因子ⅩⅢa属于普遍存在的转谷氨酰胺酶家族，该家族催化特定赖氨酸的ε-氨基与谷氨酰胺的γ-羧基之间形成共价键。凝血因子ⅩⅢ最初以酶原形式合成，激活后参与凝血和纤维蛋白溶解机制。大多数转谷氨酰胺酶存在于细胞内，但凝血因子ⅩⅢ在细胞内和细胞外均有分布。细胞外（血浆）凝血因子ⅩⅢ以非共价异源四聚体A2B2的形式存在，其生物合成过程较为复杂。本文通过聚合酶链反应（PCR）分析和Northern印迹法证明，肝脏中存在A和B亚基的信使核糖核酸（mRNA）。还分析了凝血因子ⅩⅢ亚基特异性mRNA在各种人体组织中的分布情况。在所检测的组织中，仅在肝脏中发现了B亚基的信号。对于A亚基，在胎盘、肝脏、肾脏、肺、骨骼肌和心脏中观察到强度不同的信号；在脑或胰腺中未发现信号。采用免疫过氧化物酶法在PLC/PRF/5细胞系中鉴定出凝血因子ⅩⅢ A亚基。通过酶联免疫吸附测定（ELISA）和反向免疫印迹法，使用针对A - B复合物的特异性抗体，还表明这些细胞能够产生并分泌凝血因子ⅩⅢ。根据所有这些结果，我们得出结论，肝脏是血浆凝血因子ⅩⅢ的来源，并且A2B2复合物是从这些细胞中分泌出来的。
