Platelet PECAM-1 inhibits thrombus formation in vivo.
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.
Falati
Shahrokh
S
Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Patil
Sonali
S
Gross
Peter L
PL
Stapleton
Michelle
M
Merrill-Skoloff
Glenn
G
Barrett
Natasha E
NE
Pixton
Katherine L
KL
Weiler
Harmut
H
Cooley
Brian
B
Newman
Debra K
DK
Newman
Peter J
PJ
Furie
Barbara C
BC
Furie
Bruce
B
Gibbins
Jonathan M
JM
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
D002712:Chlorides; D005290:Ferric Compounds; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C024555:ferric chloride