Turner Nancy, Nolasco Leticia, Nolasco Jennifer, Sartain Sarah, Moake Joel
Department of Bioengineering, Rice University, Houston, Texas.
Semin Thromb Hemost. 2014 Jul;40(5):544-50. doi: 10.1055/s-0034-1383547. Epub 2014 Jun 26.
Molecular linkages between von Willebrand factor (VWF) and the alternative complement pathway (AP) have recently been discovered. Endothelial cell (EC)-anchored ultra-large (UL) VWF multimeric strings function as an activating surface for the AP. C3 (in active C3b form) binds to the EC-anchored ULVWF strings, and promotes the assembly of C3bBb (C3 convertase) and C3bBbC3b (C5 convertase). These linkages may help to explain enigmatic clinical problems related to thrombotic microangiopathies, including some cases of refractory thrombotic thrombocytopenic purpura (TTP), TTP associated with only mild-modest deficiencies of ADAMTS-13, the provocation (or exacerbation) of acute episodes in patients with the atypical hemolytic uremic syndrome, and thrombosis in paroxysmal nocturnal hemoglobinuria. Recent experiments have also demonstrated that complement factor H performs a dual role: participating in regulation of the AP by binding to EC-anchored ULVWF strings; and functioning as a reductase to decrease the size of soluble VWF multimers.
最近发现了血管性血友病因子（VWF）与替代补体途径（AP）之间的分子联系。内皮细胞（EC）锚定的超大（UL）VWF多聚体链作为AP的激活表面。C3（活性C3b形式）与EC锚定的ULVWF链结合，并促进C3bBb（C3转化酶）和C3bBbC3b（C5转化酶）的组装。这些联系可能有助于解释与血栓性微血管病相关的神秘临床问题，包括一些难治性血栓性血小板减少性紫癜（TTP）病例、仅伴有轻度至中度ADAMTS-13缺乏的TTP、非典型溶血性尿毒症综合征患者急性发作的激发（或加重）以及阵发性夜间血红蛋白尿中的血栓形成。最近的实验还表明，补体因子H具有双重作用：通过与EC锚定的ULVWF链结合参与AP的调节；并作为还原酶来减小可溶性VWF多聚体的大小。
