P-Selectin-dependent inhibition of thrombosis during venous stasis.
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.
Eppihimer
M J
MJ
Wyeth/Genetics Institute, Discovery Research, Andover, Massachusetts, USA.
Schaub
R G
RG
D000818:Animals; D002415:Cats; D002448:Cell Adhesion; D002465:Cell Movement; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007275:Injections, Intravenous; D007958:Leukocyte Count; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D019007:P-Selectin / Q000502:physiology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020246:Venous Thrombosis / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*
D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D011994:Recombinant Proteins