NDLI: Antihemostatic activity of human granzyme B mediated by cleavage of von Willebrand factor.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Gardiner, Elizabeth E. Dyson, Jennifer M. Kaiserman, Dion Choi, Hiuwan Bird, Phillip I. Mitchell, Christina A. Dong, Jing-fei Andrews, Robert K. Buzza, Marguerite S. Berndt, Michael C.
Description	Author Affiliation: Buzza MS ( Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia.)
Abstract	The cytotoxic lymphocyte protease granzyme B (GrB) is elevated in the plasma of individuals with diseases that elicit a cytotoxic lymphocyte-mediated immune response. Given the recently recognized ability of GrB to cleave extracellular matrix proteins, we examined the effect of GrB on the pro-hemostatic molecule von Willebrand factor (VWF). GrB delays ristocetin-induced platelet aggregation and inhibits platelet adhesion and spreading on immobilized VWF under static conditions. It efficiently cleaves VWF at two sites within the A1-3 domains that are essential for the VWF-platelet interaction. Like the VWF regulatory proteinase ADAMTS-13, GrB-mediated cleavage is dependent upon VWF conformation. In vitro, GrB cannot cleave the VWF conformer found in solution, but cleavage is induced when VWF is artificially unfolded or presented as a matrix. GrB cleaves VWF with comparable efficiency to ADAMTS-13 and rapidly processes ultra-large VWF multimers released from activated endothelial cells under physiological shear. GrB also cleaves the matrix form of fibrinogen at several sites. These studies suggest extracellular GrB may help control localized coagulation during inflammation.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	33
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Granzymes Pharmacology Hemostasis Physiology Lymphocytes Immunology Platelet Adhesiveness Drug Effects Platelet Aggregation Von Willebrand Factor Metabolism Animals Endothelium, Vascular Fibrinogen Kinetics Lymphokines Mice Rabbits Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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