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Bile salt–dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans
Laurence Panicot-Dubois, … , Dominique Lombardo, Christophe Dubois
Laurence Panicot-Dubois, … , Dominique Lombardo, Christophe Dubois
Published November 21, 2007
Citation Information: J Clin Invest. 2007;117(12):3708-3719. https://doi.org/10.1172/JCI32655.
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Research Article Hematology

Bile salt–dependent lipase interacts with platelet CXCR4 and modulates thrombus formation in mice and humans

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Abstract

Bile salt–dependent lipase (BSDL) is an enzyme involved in the duodenal hydrolysis and absorption of cholesteryl esters. Although some BSDL is transported to blood, the role of circulating BSDL is unknown. Here, we demonstrate that BSDL is stored in platelets and released upon platelet activation. Because BSDL contains a region that is structurally homologous to the V3 loop of HIV-1, which binds to CXC chemokine receptor 4 (CXCR4), we hypothesized that BSDL might bind to CXCR4 present on platelets. In human platelets in vitro, both BSDL and a peptide corresponding to its V3-like loop induced calcium mobilization and enhanced thrombin-mediated platelet aggregation, spreading, and activated αIIbβ3 levels. These effects were abolished by CXCR4 inhibition. BSDL also increased the production of prostacyclin by human endothelial cells. In a mouse thrombosis model, BSDL accumulated at sites of vessel wall injury. When CXCR4 was antagonized, the accumulation of BSDL was inhibited and thrombus size was reduced. In BSDL–/– mice, calcium mobilization in platelets and thrombus formation were attenuated and tail bleeding times were increased in comparison with those of wild-type mice. We conclude that BSDL plays a role in optimal platelet activation and thrombus formation by interacting with CXCR4 on platelets.

Authors

Laurence Panicot-Dubois, Grace M. Thomas, Barbara C. Furie, Bruce Furie, Dominique Lombardo, Christophe Dubois

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Effect of BSDL on platelet aggregation induced by different agonists

Effect of BSDL on platelet aggregation induced by different agonists


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