title: Platelet PECAM-1 inhibits thrombus formation in vivo.
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.
authors.affiliation: Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Shahrokh
authors.initials: S
authors.lastname: Falati
authors.forename: Sonali
authors.initials: S
authors.lastname: Patil
authors.forename: Peter L
authors.initials: PL
authors.lastname: Gross
authors.forename: Michelle
authors.initials: M
authors.lastname: Stapleton
authors.forename: Glenn
authors.initials: G
authors.lastname: Merrill-Skoloff
authors.forename: Natasha E
authors.initials: NE
authors.lastname: Barrett
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Pixton
authors.forename: Harmut
authors.initials: H
authors.lastname: Weiler
authors.forename: Brian
authors.initials: B
authors.lastname: Cooley
authors.forename: Debra K
authors.initials: DK
authors.lastname: Newman
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Newman
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Furie
authors.forename: Bruce
authors.initials: B
authors.lastname: Furie
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gibbins
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D001853:Bone Marrow / Q000254:growth & development / Q000378:metabolism; D002339:Carotid Arteries / Q000166:cytology / Q000378:metabolism; D002712:Chlorides; D005260:Female; D005290:Ferric Compounds / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D013927:Thrombosis / Q000139:chemically induced / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C024555:ferric chloride