From the Department of Bioengineering, Rice University, Houston, TX (L.N., J.N., J.M.); and Department of Pulmonary Medicine, M.D. Anderson Cancer Center, Houston, TX (S.F., V.A.-K.).
Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2524-8. doi: 10.1161/ATVBAHA.113.302280. Epub 2013 Sep 5.
Ultralarge von Willebrand factor (vWF) strings are secreted by, and anchored to, stimulated human endothelial cells. A disintegrin and metalloprotease with thrombospondin domains-type 13 cleaves the ultralarge vWF strings into large soluble vWF multimers. Normal plasma contains a nonproteolytic reducing activity that subsequently rapidly diminishes the size of the large soluble vWF multimers.
The vWF reductase activity was isolated from normal cryoprecipitate-poor plasma by chromatography and identified as the complement regulatory protein, factor H (FH), by mass spectroscopy, SDS-PAGE, and monospecific anti-FH antibody. Removal of FH from partially purified vWF reductase by immunoabsorption eliminated the reducing activity, and the activity was recovered in the eluates. Recombinant human FH reduced large soluble vWF multimers in a free thiol-dependent reaction that was not inhibited by a variety of protease inhibitors.
FH contributes to the reduction of large soluble vWF multimers.
超大血管性血友病因子 (vWF) 链由受刺激的人内皮细胞分泌并锚定。解整合素金属蛋白酶 13 型可将超大 vWF 链切割成大的可溶性 vWF 多聚体。正常血浆中含有一种非蛋白水解还原活性，可随后迅速减小大的可溶性 vWF 多聚体的大小。
通过色谱法从正常无冷沉淀血浆中分离出 vWF 还原酶活性，并通过质谱、SDS-PAGE 和单特异性抗 FH 抗体鉴定为补体调节蛋白 FH。通过免疫吸附从部分纯化的 vWF 还原酶中去除 FH 可消除还原活性，且该活性可在洗脱液中回收。重组人 FH 可在游离巯基依赖性反应中还原大的可溶性 vWF 多聚体，该反应不受多种蛋白酶抑制剂的抑制。
FH 有助于还原大的可溶性 vWF 多聚体。
