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Platelet PECAM-1 inhibits thrombus formation in vivo. Blood 2006 Jan 15;107(2):535-41

Date

09/17/2005

Pubmed ID

16166583

Pubmed Central ID

PMC1895610

DOI

10.1182/blood-2005-04-1512

Scopus ID

2-s2.0-30444452396 (requires institutional sign-in at Scopus site)   182 Citations

Abstract

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell surface glycoprotein receptor expressed on a range of blood cells, including platelets, and on vascular endothelial cells. PECAM-1 possesses adhesive and signaling properties, the latter being mediated by immunoreceptor tyrosine-based inhibitory motifs present on the cytoplasmic tail of the protein. Recent studies in vitro have demonstrated that PECAM-1 signaling inhibits the aggregation of platelets. In the present study we have used PECAM-1-deficient mice and radiation chimeras to investigate the function of this receptor in the regulation of thrombus formation. Using intravital microscopy and laser-induced injury to cremaster muscle arterioles, we show that thrombi formed in PECAM-1-deficient mice were larger, formed more rapidly than in control mice, and were more stable. Larger thrombi were also formed in control mice that received transplants of PECAM-1-deficient bone marrow, in comparison to mice that received control transplants. A ferric chloride model of thrombosis was used to investigate thrombus formation in carotid arteries. In PECAM-1-deficient mice the time to 75% vessel occlusion was significantly shorter than in control mice. These data provide evidence for the involvement of platelet PECAM-1 in the negative regulation of thrombus formation.

Author List

Falati S, Patil S, Gross PL, Stapleton M, Merrill-Skoloff G, Barrett NE, Pixton KL, Weiler H, Cooley B, Newman DK, Newman PJ, Furie BC, Furie B, Gibbins JM

Authors

Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Hartmut Weiler PhD Associate Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Blood Coagulation
Blood Platelets
Bone Marrow
Carotid Arteries
Chlorides
Female
Ferric Compounds
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Platelet Endothelial Cell Adhesion Molecule-1
Thrombosis
Time Factors