ADAMTS13: A New Link Between Thrombosis and Inflammation

View/ Open
Author
Chauhan, Anil K.
Kisucka, Janka
Walsh, Meghan T.
Scheiflinger, Friedrich
Published Version
https://doi.org/10.1084/jem.20080130Metadata
Show full item recordCitation
Chauhan, Anil K., Janka Kisucka, Alexander Brill, Meghan T. Walsh, Friedrich Scheiflinger, and Denisa D. Wagner. 2008. ADAMTS13: a new link between thrombosis and inflammation. The Journal of Experimental Medicine 205(9): 2065-2074.Abstract
von Willebrand factor (VWF) levels are elevated and a disintegrin-like and metalloprotease with thrombospondin type I repeats–13 (ADAMTS13) activity is decreased in both acute and chronic inflammation. We hypothesized that by cleaving hyperactive ultralarge VWF (ULVWF) multimers, ADAMTS13 down-regulates both thrombosis and inflammation. Using intravital microscopy, we show that ADAMTS13 deficiency results in increased leukocyte rolling on unstimulated veins and increased leukocyte adhesion in inflamed veins. Both processes were dependent on the presence of VWF. Depletion of platelets in \(Adamts13^{−/−}\) mice reduced leukocyte rolling, suggesting that platelet interaction with ULVWF contributes to this process. Increased levels of endothelial P-selectin and plasma VWF in \(Adamts13^{−/−}\) compared with wild-type (WT) mice indicated an elevated release of Weibel-Palade bodies. ULVWF multimers released upon stimulation with histamine, a secretagogue of Weibel-Palade bodies, slowed down leukocyte rolling in \(Adamts13^{−/−}\) but not in WT mice. Furthermore, in inflammatory models, ADAMTS13 deficiency resulted in enhanced extravasation of neutrophils, and this process was also dependent on VWF. Our findings reveal an important role for ADAMTS13 in preventing excessive spontaneous Weibel-Palade body secretion, and in the regulation of leukocyte adhesion and extravasation during inflammation.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526201/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:5355304
Collections
- HMS Scholarly Articles [17875]
Contact administrator regarding this item (to report mistakes or request changes)