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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:372-377.)
© 1999 American Heart Association, Inc.

Original Contribution

Selectin Blockade Reduces Neutrophil Interaction With Platelets at the Site of Deep Arterial Injury by Angioplasty in Pigs

Yahye Merhi; Patrick Provost; Patrick Chauvet; Jean-François Théorêt; M. Laurie Phillips; Jean-Gilles Latour

From the Laboratory of Experimental Pathology, Montreal Heart Institute, and the University of Montreal, Montreal, Quebec, Canada (Y.M., P.P., P.C., J.F.T., J.-G.L.); and Cytel Corporation (M.L.P.), San Diego, CA.

Abstract—The adhesion of neutrophils to damaged arterial surfaces is increased in the presence of platelets by a mechanism implicating platelet P-selectin. Such interactions may enhance thrombus formation and the vascular response to injury. In this study, we investigated the effects of a selectin blocker (CY-1503), an analogue of sialyl Lewis^x, on platelet and neutrophil interactions after arterial injury produced by angioplasty in pigs.⁵¹Cr-platelet deposition and ¹¹¹In-neutrophil adhesion were quantified on intact, mildly and deeply injured carotid arterial segments, produced by balloon dilation, in control (saline, n=8) and treated (CY-1503, 15 mg/kg IV, n=7) pigs. The hematological parameters, the aggregation of whole blood in response to adenosine diphosphate, and the activating clotting time, as well as the heart rate and mean arterial blood pressure, were similar among groups and were not influenced significantly by CY-1503. The level of platelet and neutrophil adhesion increased significantly with the severity of arterial injury but was not influenced by CY-1503 on intact and mildly injured arterial segments. However, at the site of deep arterial injury, CY-1503 treatment was associated with a 58% reduction (P<0.01) in neutrophil adhesion, from 446.7±72.6x10³ neutrophils/cm² in the control group to 186.8±38.7x10³ neutrophils/cm² in the CY-1503–treated group, whereas platelet deposition remained unchanged (43.4±15.6x10⁶ platelets/cm² versus 50.1±12.2x10⁶ platelets/cm² in the control group). In in vitro adhesion experiments, using isolated platelet and neutrophil suspensions, we found that CY-1503 interfered with the adhesion of neutrophils to damaged arterial surfaces only in the presence of platelets. In contact with thrombogenic arterial surfaces, adherent and activated platelets supports neutrophil adhesion at the site of deep injury by an adhesive interaction involving neutrophil sialyl Lewis^x. The inhibitory effect of CY-1503 on neutrophil interaction with adherent platelets may be clinically relevant in patients undergoing percutaneous transluminal coronary angioplasty where platelet and neutrophil interactions may enhance the acute and chronic arterial response to injury.

Key Words: platelets • neutrophils • angioplasty • selectin • CY-1503

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