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. Research Abstract Details 

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

Li Zhu,Wolfgang Bergmeier,Jie Wu,Hong Jiang,Timothy J Stalker,Marcin Cieslak,Ran Fan,Laurence Boumsell,Atsushi Kumanogoh,Hitoshi Kikutani,Luca Tamagnone,Denisa D Wagner,Marcos E Milla,Lawrence F Brass,

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.

Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Publishing Authors By Initials

L Zhu,W Bergmeier,J Wu,H Jiang,TJ Stalker,M Cieslak,R Fan,L Boumsell,A Kumanogoh,H Kikutani,L Tamagnone,DD Wagner,ME Milla,LF Brass,

For similar cardiovascular diseases: vascular diseases: embolism and thrombosis: thrombosis research abstracts see: cardiovascular diseases: vascular diseases: embolism and thrombosis: thrombosis research

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 1621-6

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 23

MONTH: 01

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Keywords Mesh Terms:

KEYWORDS: Thrombosis

MESH TERMS: metabolism

Chemical & Substance for Abstract: Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Information

Substance Name: tumor necrosis factor-alpha convertase

Registry Number: EC 3.4.24.-

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

AFFILIATION: Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL81012

ACRONYM: HL

MEDLINETA: Proc Natl Acad Sci U S A

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