Endothelial cell-derived high molecular weight von Willebrand factor is converted into the plasma multimer pattern by granulocyte proteases.

Abstract

We have previously found that the von Willebrand factor released by cultured human umbilical vein endothelial cells appeared as a single high molecular weight band in glyoxyl agarose electrophoresis. In the present studies we report that this high molecular weight endothelial cell-derived von Willebrand factor, when incubated with granulocyte lysates, was cleaved into a series of multimers indistinguishable from those seen in normal plasma (or type II von Willebrand disease). This von Willebrand factor-cleaving activity was released from granulocytes by calcium ionophore A23187 but was not detected in cytosolic fractions depleted of granular contents. It was inhibited by the serine protease inhibitor phenylmethylsulfonyl fluoride. This von Willebrand factor-cleaving activity thus provides a possible mechanism for the generation of plasma von Willebrand factor multimers from the high molecular weight form of von Willebrand factor secreted by endothelial cells.

• Authors: H M Tsai, R L Nagel, V B Hatcher, I I Sussman
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 158 Issue 3 Pg. 980-5 (Feb 15 1989) ISSN: 0006-291X [Print] United States
• PMID: 2493251 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Macromolecular Substances
• Protease Inhibitors
• von Willebrand Factor
• Isoflurophate
• Calcimycin
• Phenylmethylsulfonyl Fluoride
• Peptide Hydrolases

Topics

• Calcimycin (pharmacology)
• Cells, Cultured
• Endothelium, Vascular (metabolism)
• Granulocytes (drug effects, enzymology)
• Humans
• Isoflurophate (pharmacology)
• Macromolecular Substances
• Molecular Weight
• Peptide Hydrolases (metabolism)
• Phenylmethylsulfonyl Fluoride (pharmacology)
• Protease Inhibitors (pharmacology)
• Umbilical Veins
• von Willebrand Factor (metabolism)