Transferrin: a blood coagulation modifier.
Transferrin: a blood coagulation modifier.
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转铁蛋白：一种凝血调节剂。
DOI：
10.1038/s41422-020-0275-z
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发表时间：
2020
期刊：
影响因子：
44.1
通讯作者：
Schmaier,AlvinH
中科院分区：
文献类型：
--
作者：
Schmaier,AlvinH
哺乳动物血液凝固系统的蛋白质是一组蛋白质和调节剂，其主要工作是止血，存在于血浆血管区室中，并有机会与多种其他蛋白质相互作用。Tang等人的文章提出了新的观察结果，即转铁蛋白是一种铁转运蛋白，存在于血浆中，其浓度超过所有凝血蛋白，通过增加凝血酶和因子XIIa活性并抑制抗凝血酶来促进血液凝固。血液凝固系统的主要功能是控制出血，即止血，由核心组的酶原组成（因子XII、前激肽释放酶、因子XI、因子IX、因子VII、因子X、凝血酶原）、辅因子和底物（高分子量激肽原、因子VIII、组织因子、因子V、蛋白S和纤维蛋白原）、凝块溶解（纤维蛋白溶解）剂（纤溶酶原、组织和尿激酶纤溶酶原激活剂）和调节剂（抗凝血酶（AT）、C1抑制剂、α-2-抗纤溶酶、蛋白C、纤溶酶原激活物抑制剂和组织因子途径抑制剂）（图1）。这些蛋白质的缺陷或缺陷导致出血或影响血栓形成的风险。大多数人认为该过程是一个孤立的系统，其激活通过线性级联中的两种途径（组织因子-因子VIIa或接触激活）进行。然而，该系统存在于血浆的血管内隔室中，血浆是充满肝脏和其他细胞分泌的蛋白质产物的蛋白质液体。已经认识到血浆蛋白玻连蛋白、富含组氨酸的糖蛋白、髓样相关蛋白8-14、淀粉样前体蛋白、C反应蛋白和β-2-糖蛋白1影响血栓形成风险，但不影响止血。止血修饰剂较少被认可。转铁蛋白是一种80 kDa的铁转运蛋白，存在于血浆中，浓度为25-45 μM，超过所有凝血蛋白和抑制剂的总和。1转铁蛋白在肝脏、精液和脑脊液中产生。虽然转铁蛋白结合铁占体内总铁的< 1%，但转铁蛋白是参与铁代谢的最重要的蛋白质。转铁蛋白结合铁是一个铁池，每天的最高营业额，25毫克/24小时。游离转铁蛋白（脱铁转铁蛋白）以高亲和力结合2个不溶性铁3+原子进行可溶性转运;低pH值（5.6）降低亲和力，允许铁释放到其受体。高转铁蛋白水平发生在缺铁、怀孕和口服避孕药时，表明需要结合更多的铁。或者，在慢性炎症状态下，转铁蛋白水平下降。转铁蛋白是先天免疫系统的成员;它在结合铁后阻碍细菌存活。血清中的非转铁蛋白结合铁（NTBI）与血管炎症相关，其特征在于低密度脂蛋白氧化，血管活性氧增加，透化，持续的内皮细胞活化，NO产生减少，
The proteins of the mammalian blood coagulation system, a group of proteins and regulators whose major job is to stop bleeding, exist in the plasma vascular compartment and have opportunity to interact with multiple other proteins. The article by Tang et al. presents the novel observation that transferrin, an iron transport protein that exists in plasma in concentration excess to all the blood coagulation proteins, promotes blood coagulation by increasing thrombin and factor XIIa activities and inhibiting antithrombin.The blood coagulation system whose major function is to control bleeding, ie, hemostasis, consists of a core group of proenzymes (factor XII, prekallikrein, factor XI, factor IX, factor VII, factor X, prothrombin), cofactors and substrates (high molecular weight kininogen, factor VIII, tissue factor, factor V, protein S, and fibrinogen), clot lysing (fibrinolytic) agents (plasminogen, tissue and urokinase plasminogen activators), and regulators (antithrombin (AT), C1 inhibitor, α-2-antiplasmin, protein C, plasminogen activator inhibitor, and tissue factor pathway inhibitor)(Fig. 1). Deficiencies or defects in these proteins lead to bleeding or influence thrombosis risk. Most think of the process as an isolated system whose activation proceeds through two pathways (tissue factor-factor VIIa or contact activation) in a linear cascade. However, this system exists in the intravascular compartment in blood plasma, a proteinaceous fluid filled with the secreted protein products of the liver and other cells. It has been recognized that the plasma proteins vitronectin, histidine-rich glycoprotein, myeloid-related protein 8-14, amyloid precursor protein, C-reactive protein, and β-2-glycoprotein 1, influence thrombosis risk without effect on hemostasis. Modifiers of hemostasis are less recognized. Transferrin is an 80kDa iron transport protein that exists in plasma at a concentration of 25-45 μM, a value in excess of the sum of all the coagulation proteins and inhibitors. 1 Transferrin is produced in the liver, semen, and cerebrospinal fluid. Although transferrin-bound iron accounts for< 1% of total iron in the body, transferrin is the most vital protein involved in iron metabolism. Transferrin-bound iron is a pool of iron with the daily highest turnover, 25 mg/24 h. Free transferrin (apotransferrin) binds with high affinity 2 insoluble ferric3+ atoms for soluble transport; low pH (5.6) reduces affinity allowing for iron release to its receptor. High transferrin levels occur with iron deficiency, pregnancy, and oral contraceptives, indicating the need to bind more iron. Alternatively, in chronic inflammatory states, transferrin levels fall. Transferrin is a member of the innate immune system; it impedes bacterial survival upon binding iron. Non-transferrin-bound iron (NTBI) in serum is associated with vascular inflammation characterized by low-density lipoprotein oxidation, increased vascular reactive oxygen species, permeabilization, sustained endothelial cell activation, reduced NO production with impaired