Platelet PECAM-1 inhibits thrombus formation in vivo
Falati, S., Patil, S., Gross, P. L., Stapleton, M., Merrill-Skoloff, G., Barrett, N. E., Pixton, K. L., Weiler, H., Cooley, B., Newman, D. K., Newman, P. J., Furie, B. C., Furie, B. and Gibbins, J. M. (2006) Platelet PECAM-1 inhibits thrombus formation in vivo. Blood, 107 (2). pp. 535-541. ISSN 0006-4971
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To link to this article DOI: 10.1182/blood-2005-04-1512
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.