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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2483.)
© 2000 American Heart Association, Inc.

Thrombosis

P-Selectin–Dependent Inhibition of Thrombosis During Venous Stasis

Michael J. Eppihimer; Robert G. Schaub

From the Wyeth/Genetics Institute, Discovery Research, Immunology (M.J.E.) and Hemostasis (R.G.S.), Andover, Mass.

Correspondence to Michael J. Eppihimer, PhD, Wyeth/Genetics Institute, Inc, Discovery Research, Immunology and Hemostasis, One Burtt Rd, Andover, MA 01810.

Abstract—Leukocyte adhesion, transendothelial migration, and stasis are important components in the pathogenesis of deep vein thrombosis. Anesthetized cats were treated with saline, a recombinant soluble form of P-selectin glycoprotein ligand-1 (rPSGL-Ig), or an E- and L-selectin antibody (EL-246) before exposure and occlusion of a jugular vein. After 2 or 6 hours of occlusion, jugular veins were perfused with buffer, fixed, and prepared for scanning electron microscopy. In cats receiving saline, 2 and 6 hours of occlusion produced moderate levels of leukocyte and platelet adhesion and endothelial cell injury. Treatment of cats with rPSGL-Ig or EL-246 had no apparent effect on the magnitude of cell adhesion and endothelial cell injury compared with no treatment. After 6 hours of occlusion, the presence of a mural thrombus in untreated veins was observed and confirmed by scanning electron microscopy. Pretreatment of cats with rPSGL-Ig completely (4.0 mg/kg) or partially (1.0 mg/kg) prevented the occurrence of thrombi in the jugular veins. The reduction in thrombosis by rPSGL-Ig treatment after 6 hours of venous stasis, in the absence of any effect on leukocyte-mediated endothelial cell injury, suggests an antithrombotic mechanism of action for this protein.

Key Words: leukocytes • platelets • endothelial cells • thrombosis • selectin

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