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Blood, 15 January 2006, Vol. 107, No. 2, pp. 535-541.
Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-04-1512.
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Submitted April 14, 2005
Accepted September 2, 2005
Platelet PECAM-1 inhibits thrombus formation in vivo
Shahrokh Falati, Sonali Patil, Peter L Gross, Michelle Stapleton, Glenn Merrill-Skoloff, Natasha E Barrett, Katherine L Pixton, Harmut Weiler, Brian Cooley, Debra K Newman, Peter J Newman, Barbara C Furie, Bruce Furie, and Jonathan M Gibbins*
Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA
Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
School of Biological Sciences, The University of Reading, Reading, Berkshire, United Kingdom
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
Department of Orthopaedics, Medical College of Wisconsin, Milwaukee, WI, USA
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA; Department of Microbiology, Medical College of Wisconsin, Milwaukee, WI, USA
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA; Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Cellular Biology, Medical College of Wisconsin, Milwaukee, WI, USA
* Corresponding author; email: j.m.gibbins{at}reading.ac.uk.
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell surface glycoprotein receptor expressed on a range of blood cells including platelets, and is also on vascular endothelial cells. PECAM-1 possesses adhesive and signalling properties, the latter being mediated by an Immunoreceptor Tyrosine-based Inhibitory Motif present on the cytoplasmic tail of the protein. Recent studies in vitro have demonstrated that PECAM-1 signalling inhibits the aggregation of platelets. In the present study we have utilised 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 transplanted with PECAM-1 deficient bone marrow, in comparison to control transplanted mice. 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.
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