Factor XII-independent activation of factor XI in plasma: effects of sulfatides on tissue factor-induced coagulation.
Factor XII-independent activation of factor XI in plasma: effects of sulfatides on tissue factor-induced coagulation.
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DOI：
10.1182/blood.v82.3.813.813
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发表时间：
1993-08
期刊：
影响因子：
20.3
通讯作者：
D. Gailani;G. Broze
中科院分区：
文献类型：
--
作者：
D. Gailani;G. Broze
因子XI（FXI）可以在纯化的系统中通过凝血酶和在带负电荷的物质如硫酸葡聚糖或硫苷脂的存在下通过自活化来活化。进行当前研究以确定这些过程是否发生在血浆凝固期间。用125 I-FXI补充FXII-缺陷血浆，并用组织因子和/或硫苷脂诱导凝块形成。通过标准聚丙烯酰胺凝胶电泳和放射自显影研究FXI的切割。单独与硫苷孵育20分钟后检测到活化的FXI（FXIa），加入组织因子（TF）可显著加速该过程。TF的增强作用被水蛭素阻断，表明凝血酶参与了FXI的激活。使用3 H-FIX活化肽释放试验研究了FXIa对该系统中FIX活化的贡献。在用TF诱导凝血的血浆中，硫酸脂使FIX活化增加约两倍，但如果血浆中FXI免疫耗竭，则无影响。如果存在硫苷脂，则在用FXa诱导凝血的血浆中FIX活化也增加。FIXa的产生依赖于FXI，并被水蛭素阻断。在与硫苷脂和水蛭素的反应中观察到一些活化，可能仅由FXI自活化引起。数据表明，在存在硫苷脂的情况下血浆凝固期间，FXI通过凝血酶依赖性机制激活，不需要FXII。
Factor XI (FXI) may be activated in a purified system by thrombin and by autoactivation in the presence of negatively charged substances such as dextran sulfate or sulfatides. The current studies were performed to determine if these processes occur during the coagulation of plasma. FXII--deficient plasma was supplemented with 125I-FXI and clot formation was induced with tissue factor and/or sulfatides. Cleavage of FXI was studied by standard polyacrylamide gel electrophoresis and autoradiography. Activated FXI (FXIa) was detected after 20 minutes of incubation with sulfatides alone and this process was markedly accelerated by the addition of tissue factor (TF). The enhancing effect of TF was blocked by hirudin, which indicated thrombin involvement in FXI activation. The contribution of FXIa to FIX activation in this system was studied using a 3H-FIX activation peptide release assay. Sulfatides increased FIX activation about twofold in plasma induced to clot with TF but had no effect if the plasma was immunodepleted of FXI. FIX activation was also increased in plasma induced to clot with FXa if sulfatides were present. The enhanced generation of FIXa was dependent on FXI and was blocked by hirudin. Some activation was seen in the reactions with sulfatides and hirudin and is likely solely caused by FXI autoactivation. The data indicate that during the coagulation of plasma in the presence of sulfatides, FXI is activated by a mechanism that is thrombin dependent and does not require FXII.