Glycoprotein VI–dependent and –independent pathways of thrombus formation in vivo

Dubois, Christophe; Panicot‐Dubois, Laurence; Merrill-Skoloff, Glenn; Furie, Bruce; Furie, Barbara C.

doi:10.1182/blood-2005-09-3687

Cited by 204 publications

(269 citation statements)

References 30 publications

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“…The mice also display resistance to thrombosis in two distinct vascular injury models, one in a mediumsized artery (the carotid) exposed externally to FeCl 3 and the other in a cremaster muscle arteriole exposed from within to light-excited Rose Bengal. The thrombotic response to injuries caused by FeCl 3 has been shown to be collagen-dependent (33). In lymphocytes, sema4D on T cells promotes B cell receptor signaling by binding to CD72.…”

Section: Discussionmentioning

confidence: 99%

Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury

Zhu¹,

Bergmeier

Wu³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

176

221

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Semaphorin 4D (sema4D; CD100) is an integral membrane protein and the ligand for two receptors, CD72 and plexin-B1. Soluble sema4D has been shown to evoke angiogenic responses from endothelial cells and impair monocyte migration, but the origin of soluble sema4D, particularly at sites of vascular injury, has been unclear. Here we show that platelets express sema4D and both of its receptors and provide evidence that these molecules promote thrombus formation. We also show that the surface expression of sema4D and CD72 increases during platelet activation, followed by the gradual shedding of the sema4D extracellular domain. Shedding is blocked by metalloprotease inhibitors and abolished in mouse platelets that lack the metalloprotease ADAM17 (TACE). Mice that lack sema4D exhibit delayed arterial occlusion after vascular injury in vivo, and their platelets show impaired collagen responses in vitro. In resting platelets, as in B lymphocytes, CD72 is associated with the protein tyrosine phosphatase SHP-1. Platelet activation causes dissociation of the complex, as does the addition of soluble sema4D. These findings suggest a dual role for sema4D in vascular responses to injury. As thrombus formation begins, platelet-associated sema4D can bind to its receptors on nearby platelets, promoting thrombus formation. As thrombus formation continues, sema4D is shed from the platelet surface and becomes available to interact with receptors on endothelial cells and monocytes, as well as continuing to interact with platelets.signaling ͉ thrombosis ͉ metalloprotease ͉ CD72 ͉ plexin-B1 P latelet activation typically begins with the exposure of collagen within a damaged vessel wall or the local generation of thrombin, but the establishment of a stable thrombus requires the recruitment of additional platelets and the development of stable contacts between platelets (1). Platelet activation also results in the release from platelets of molecules that can affect nearby cells, including endothelial cells and leukocytes as well as other platelets. In a continuing search for molecules that might contribute to contact-dependent events during thrombus formation, we screened human platelets for members of the semaphorin family. Although sempahorins are best known as regulators of neurite outgrowth and vascular development, individual family members have been shown to participate in a variety of events. Class IV semaphorin [semaphorin 4D (sema4D; CD100)] is a type I integral membrane protein first reported on T cells where it supports B cell development by binding to CD72 (2-4). However, sema4D receptors are not limited to B cells. Prior work has shown that a soluble sema4D extracellular domain fragment can activate endothelial cells by its other known receptor, plexin-B1. This causes endothelial migration, actin rearrangement, and the formation of tube-like structures in vitro, responses that are relevant for wound healing and angiogenesis (5-11). Soluble sema4D has also been shown to inhibit monocyte (12) and dendritic cell (13) migration. ...

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Section: Discussionmentioning

confidence: 99%

Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury

Zhu¹,

Bergmeier

Wu³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

176

221

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“…We have previously shown that thrombin is the major platelet agonist involved in thrombus formation following laser-induced injury under our conditions (35). To exclude the possibility that thrombin generation was defective in BSDL-null mice in comparison with wild-type mice, fibrin accumulation at the site of injury was compared in BSDL-null and wild-type mice.…”

Section: Conditionsmentioning

confidence: 99%

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

Panicot‐Dubois¹,

Thomas²,

Furie³

et al. 2007

J. Clin. Invest.

Self Cite

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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 α IIb β 3 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.

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“…This system was appropriate for our purposes because the consequences of FeCl 3 treatment of mouse mesentery are known. First, FeCl 3 treatment causes denudation of the arterial endothelium and the coincident exposure of what appears to be VWF 44 and collagen 45 of the subendothelium, thereby generating a thrombogenic surface. Second, VWF is the dominant molecule involved in platelet deposition on the damaged endothelium of FeCl 3 -treated vessels.…”

Section: Gpib-dependent Fecl 3 -Induced Stable Occlusion Of the Carotmentioning

confidence: 99%

Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo

Liu

Fitzgerald

Berndt

et al. 2006

Blood

129

113

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Glycoprotein VI–dependent and –independent pathways of thrombus formation in vivo

Abstract: The role of the collagen receptor glycoprotein VI (GPVI) in arteriolar thrombus formation was studied in FcR␥-null mice (FcR␥ ؊/؊ ) lacking platelet surface GPVI.

Cited by 204 publications

References 30 publications

Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury

Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury

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

Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo

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