Journal article
ADAMTS13: a new link between thrombosis and inflammation
The Journal of experimental medicine, Vol.205(9), pp.2065-2074
09/01/2008
DOI: 10.1084/jem.20080130
PMCID: PMC2526201
PMID: 18695007
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.
Details
- Title: Subtitle
- ADAMTS13: a new link between thrombosis and inflammation
- Creators
- Anil K Chauhan - Immune Disease Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115Janka Kisucka - Immune Disease Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115Alexander Brill - Immune Disease Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115Meghan T Walsh - Immune Disease InstituteFriedrich Scheiflinger - Baxter Bioscience, 1220 Vienna, AustriaDenisa D Wagner - Immune Disease Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.205(9), pp.2065-2074
- DOI
- 10.1084/jem.20080130
- PMID
- 18695007
- PMCID
- PMC2526201
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 09/01/2008
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094396702771
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