ADAMTS13: A New Link Between Thrombosis and Inflammation

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ADAMTS13: A New Link Between Thrombosis and Inflammation

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Title: ADAMTS13: A New Link Between Thrombosis and Inflammation
Author: Chauhan, Anil K.; Kisucka, Janka; Walsh, Meghan T.; Scheiflinger, Friedrich; Brill, Alexander; Wagner, Denisa D.

Note: Order does not necessarily reflect citation order of authors.

Citation: 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.
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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.
Published Version: doi:10.1084/jem.20080130
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#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:5355304

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