ROLE OF PLATELET-ENDOTHELIAL CELL-ADHESION MOLECULE (PECAM) IN PLATELET-ADHESION AGGREGATION OVER INJURED BUT NOT DENUDED ENDOTHELIUM IN-VIVO AND EX-VIVO

Background and Purpose We previously demonstrated that a monoclonal an tibody (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 e xposure of collagen or basal lamina at the injured site, and the modul ation of adhesion/aggregation at such sites has not received much stud y. The present investigation attempted to replicate the first with the use of a different MoAb, definitely characterized as anti-PECAM. In a ddition, 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 M oAb on the platelets rather than on the endothelium. Methods A helium- neon laser, in the presence of intravascular Evans blue, was used to i njure the endothelium of arterioles on the surface of the mouse brain. Intravital microscopy was used to determine the number of seconds req uired for the light to initiate the first recognizable platelet aggreg ate forming at the injured site. Mice injected with vehicle were compa red with mice injected with 2 mg/kg anti-PECAM through the tail vein. The injection was 10 minutes before challenge with the laser. Addition al studies were performed of aggregation produced in vitro by arachido nate and by ADP added to platelet-rich plasma (PRP) prepared from bloo d taken from MoAb-treated and vehicle-treated mice. Results Aggregatio n latency was significantly prolonged (P<.02) by anti-PECAM (121+/-59 versus 65+/-26 seconds in controls; n=10 each). Aggregation ex vivo wa s not affected. Conclusions PECAM is an important modulator of platele t adhesion/aggregation at sites of minor endothelial damage in brain a rterioles. The data are consistent with the hypothesis that PECAM site s on the endothelium are involved and may be exposed by the injury to promote adhesion/aggregation. Since the endothelial cell layer is inta ct at these sites, mechanisms such as this offer important alternative s to the more commonly studied pathways of platelet activation, which require exposure of collagen and are not applicable in this model.