ADAMTS13: a new link between thrombosis and inflammation
Anil K Chauhan1, Janka Kisucka, Alexander Brill
1Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
The Journal of Experimental Medicine
|August 13, 2008
Summary
The enzyme ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) regulates inflammation by cleaving ultralarge von Willebrand factor (VWF) multimers, preventing excessive leukocyte adhesion and extravasation.
Area of Science:
- Hematology
- Immunology
- Biochemistry
Background:
- Elevated von Willebrand factor (VWF) and decreased ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) activity are observed in inflammatory conditions.
- Ultralarge VWF (ULVWF) multimers are implicated in thrombosis and inflammation.
Purpose of the Study:
- To investigate the role of ADAMTS13 in cleaving ULVWF multimers and its impact on thrombosis and inflammation.
- To determine if ADAMTS13 down-regulates leukocyte adhesion and extravasation during inflammation.
Main Methods:
- Intravital microscopy in wild-type (WT) and Adamts13(-/-) mice.
- Platelet depletion experiments.
- Measurement of endothelial P-selectin and plasma VWF levels.
- Histamine stimulation to assess Weibel-Palade body release.
- Evaluation of neutrophil extravasation in inflammatory models.
Main Results:
- ADAMTS13 deficiency led to increased leukocyte rolling and adhesion, dependent on VWF.
- Platelet depletion reduced leukocyte rolling in Adamts13(-/-) mice.
- Adamts13(-/-) mice exhibited elevated P-selectin and VWF, indicating increased Weibel-Palade body release.
- Neutrophil extravasation was enhanced in Adamts13(-/-) mice during inflammation.
Conclusions:
- ADAMTS13 plays a crucial role in preventing spontaneous Weibel-Palade body secretion.
- ADAMTS13 regulates leukocyte adhesion and extravasation during inflammation by cleaving ULVWF.
- These findings highlight ADAMTS13 as a potential therapeutic target for inflammatory and thrombotic disorders.
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