title: Human complement factor H is a reductase for large soluble von Willebrand factor multimers--brief report.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  FH contributes to the reduction of large soluble vWF multimers.
authors.affiliation: 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.).
authors.forename: Leticia
authors.initials: L
authors.lastname: Nolasco
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nolasco
authors.forename: Shuju
authors.initials: S
authors.lastname: Feng
authors.forename: Vahid
authors.initials: V
authors.lastname: Afshar-Kharghan
authors.forename: Joel
authors.initials: J
authors.lastname: Moake
mesh_terms: D017242:Complement Factor H / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008970:Molecular Weight; D010088:Oxidoreductases / Q000378:metabolism*; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: C493495:CFH protein, human; D013438:Sulfhydryl Compounds; D014841:von Willebrand Factor; D017242:Complement Factor H; D010088:Oxidoreductases; C421906:vWF reductase
keywords: complement factor H; oxidoreductases; von Willebrand factor