(Stroke. 1996;27:709-711.)
© 1996 American Heart Association, Inc.
Articles |
Role of Platelet-Endothelial Cell Adhesion Molecule (PECAM) in Platelet Adhesion/Aggregation Over Injured but Not Denuded Endothelium In Vivo and Ex Vivo
From the Division of Neuropathology, Medical College of Virginia/Virginia Commonwealth University, Richmond (W.I.R., G.H.N., B.W.), and PharMingen, San Diego, Calif (P.W., J.W., C.C.-Y.S.).
Background and Purpose We previously demonstrated that a monoclonal antibody (MoAb) with anti-CD31, anti-platelet-endothelial cell adhesion molecule (PECAM)-like properties delayed platelet adhesion/aggregation at a site of minor endothelial injury. To our knowledge, this was the first in vivo demonstration of an effect of anti-CD31. There was no exposure of collagen or basal lamina at the injured site, and the modulation of adhesion/aggregation at such sites has not received much study. The present investigation attempted to replicate the first with the use of a different MoAb, definitely characterized as anti-PECAM. In addition, an ex vivo investigation was performed to see whether the in vivo action of anti-PECAM could have been caused by an effect of the MoAb on the platelets rather than on the endothelium.
Methods A helium-neon laser, in the presence of intravascular Evans blue, was used to injure the endothelium of arterioles on the surface of the mouse brain. Intravital microscopy was used to determine the number of seconds required for the light to initiate the first recognizable platelet aggregate forming at the injured site. Mice injected with vehicle were compared with mice injected with 2 mg/kg anti-PECAM through the tail vein. The injection was 10 minutes before challenge with the laser. Additional studies were performed of aggregation produced in vitro by arachidonate and by ADP added to platelet-rich plasma (PRP) prepared from blood taken from MoAb-treated and vehicle-treated mice.
Results Aggregation latency was significantly prolonged (P<.02) by anti-PECAM (121±59 versus 65±26 seconds in controls; n=10 each). Aggregation ex vivo was not affected.
Conclusions PECAM is an important modulator of platelet adhesion/aggregation at sites of minor endothelial damage in brain arterioles. The data are consistent with the hypothesis that PECAM sites on the endothelium are involved and may be exposed by the injury to promote adhesion/aggregation. Since the endothelial cell layer is intact at these sites, mechanisms such as this offer important alternatives to the more commonly studied pathways of platelet activation, which require exposure of collagen and are not applicable in this model.
Key Words: cerebral arteries • endothelium • platelet aggregation • mice
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