Selectin blockade reduces neutrophil interaction with platelets at the site of deep arterial injury by angioplasty in pigs

The adhesion of neutrophils to damaged arterial surfaces is increased in th e presence of platelets by a mechanism implicating platelet P-selectin. Suc h interactions may enhance thrombus formation and the vascular response to injury. In this study, we investigated the effects of a selectin blocker (C Y-1503), an analogue of sialyl Lewis", on platelet and neutrophil interacti ons after arterial injury produced by angioplasty in pigs, Cr-51-platelet d eposition and In-111-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 t o adenosine diphosphate, and the activating clotting time, as well as the h eart rate and mean arterial blood pressure, were similar among groups and w ere not influenced significantly by CY-1503. The level of platelet and neut rophil adhesion increased significantly with the severity of arterial injur y but was not influenced by CY-1503 on intact and mildly injured arterial s egments. However, at the site of deep arterial injury, CY-1503 treatment wa s associated with a 58% reduction (P < 0.01) in neutrophil adhesion, from 4 46.7 +/- 72.6 x 10(3) neutrophils/cm(2) in the control group to 186.8 +/- 3 8.7 x 10(3) neutrophils/cm(2) in the CY-1503-treated group, whereas platele t deposition remained unchanged (43.4 +/- 15.6 x 10(6) platelels/cm(2) vers us 50.1 +/- 12.2 x 10(6) platelets/cm(2) 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 damage d arterial surfaces only in the presence of platelets. In contact with thro mbogenic arterial surfaces, adherent and activated platelets supports neutr ophil adhesion at the site of deep injury by an adhesive interaction involv ing neutrophil sialyl Lewis". The inhibitory effect of CY-1503 on neutrophi l interaction with adherent platelets may be clinically relevant in patient s undergoing percutaneous transluminal coronary angioplasty when platelet a nd neutrophil interactions may enhance the acute and chronic arterial respo nse to injury.