ADAMTS13: A New Link Between Thrombosis and Inflammation

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ADAMTS13: A New Link Between Thrombosis and Inflammation

Show simple item record Chauhan, Anil K. Kisucka, Janka Walsh, Meghan T. Scheiflinger, Friedrich Brill, Alexander Wagner, Denisa D. 2011-11-29T16:13:49Z 2008
dc.identifier.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. en_US
dc.identifier.issn 0022-1007 en_US
dc.description.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. en_US
dc.language.iso en_US en_US
dc.publisher The Rockefeller University Press en_US
dc.relation.isversionof doi:10.1084/jem.20080130 en_US
dc.relation.hasversion en_US
dash.license LAA
dc.title ADAMTS13: A New Link Between Thrombosis and Inflammation en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal The Journal of Experimental Medicine en_US Wagner, Denisa D. 2011-11-29T16:13:49Z
dash.affiliation.other HMS^Pathology en_US

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