Single injection of P-selectin or P-selectin glycoprotein ligand-1 monoclonal antibody blocks neointima formation after arterial injury in apolipoprotein E-deficient mice.
BACKGROUND
Emerging data suggest that P-selectin, by controlling adhesion of white blood cells, may be important in limiting the response to vascular injury.


RESULTS
We tested the hypothesis that transient inhibition of P-selectin with either anti-P-selectin monoclonal antibody (mAb) or anti-P-selectin glycoprotein ligand-1 (PSGL-1) mAb would reduce neointima formation in the setting of carotid denudation injury in atherosclerosis-prone apolipoprotein E-/- mice. Neointima formation at 28 days was reduced significantly, by 50% or 80%, by a single injection on the day of injury of 100 or 200 microg P-selectin mAb RB 40.34 and by 55% by a single injection of 100 microg PSGL-1 mAb 4RA10 (P< or =0.005). In addition, there was a significant reduction in neointimal macrophage content.


CONCLUSIONS
These findings demonstrate that transient P-selectin or PSGL-1 blockade at the time of arterial injury significantly limits plaque macrophage content and neointima formation in a dose-dependent manner after carotid denudation injury in apolipoprotein E-/- mice.
Phillips
J William
JW
Department of Medicine, Cardiovascular Division, University of Virginia Health System, Box 800158, Charlottesville, VA 22908-0158, USA.
Barringhaus
Kurt G
KG
Sanders
John M
JM
Hesselbacher
Sean E
SE
Czarnik
Ann C
AC
Manka
David
D
Vestweber
Dietmar
D
Ley
Klaus
K
Sarembock
Ian J
IJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics*; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000473:pathology / Q000628:therapy*; D001772:Blood Cell Count; D005260:Female; D005434:Flow Cytometry; D007267:Injections; D008074:Lipoproteins / Q000097:blood; D008264:Macrophages / Q000166:cytology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein