Cloning, expression, and functional characterization of the von Willebrand factor–cleaving protease (ADAMTS13)

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  • Barbara Plaimauer
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Klaus Zimmermann
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Dirk Völkel
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Gerhard Antoine
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Randolf Kerschbaumer
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Pegah Jenab
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Miha Furlan
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Helen Gerritsen
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Bernhard Lämmle
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Hans Peter Schwarz
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.
  • Friedrich Scheiflinger
    From Baxter BioScience, Biomedical Research Center, Orth, Austria; and Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.

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Description

<jats:p>Deficient von Willebrand factor (VWF) degradation has been associated with thrombotic thrombocytopenic purpura (TTP). In hereditary TTP, the specific VWF-cleaving protease (VWF-cp) is absent or functionally defective, whereas in the nonfamilial, acquired form of TTP, an autoantibody inhibiting VWF-cp activity is found transiently in most patients. The gene encoding for VWF-cp has recently been identified as a member of the metalloprotease family and designatedADAMTS13, but the functional activity of the ADAMTS13 gene product has not been verified. To establish the functional activity of recombinant VWF-cp, we cloned the complete cDNA sequence in a eukaryotic expression vector and transiently expressed the encoded recombinant ADAMTS13 in HEK 293 cells. The expressed protein degraded VWF multimers and proteolytically cleaved VWF to the same fragments as those generated by plasma VWF-cp. Furthermore, recombinant ADAMTS13-mediated degradation of VWF multimers was entirely inhibited in the presence of plasma from a patient with acquired TTP. These data show that ADAMTS13 is responsible for the physiologic proteolytic degradation of VWF multimers.</jats:p>

Journal

  • Blood

    Blood 100 (10), 3626-3632, 2002-11-15

    American Society of Hematology

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