EXOGENOUS XANTHINE PROMOTES NEUTROPHIL ADHERENCE TO CULTURED ENDOTHELIAL-CELLS

Oxidants generated by endothelial xanthine oxidase (XO) can help trigg er free radical-mediated tissue injury. An important event in oxidant- mediated tissue injury is neutrophil-endothelial adhesion. Although ac tivation of endothelial XO increases adhesion, little is known about x anthine in the adhesive effect of XO. This study examined administered xanthine on the adhesion of neutrophils. Endothelial [human umbilical vein endothelial cells (HUVEC)] monolayers were exposed to xanthine ( 15 min), and neutrophils were allowed to adhere to HUVEC in an adhesio n assay. Adhesion was dose dependently increased by xanthine (3-100 mu M). Either catalase (1,000 U/ml), oxypurinol (XO inhibitor; 100 mu M) , or platelet-activating factor (PAF) receptor antagonist (WEB 2086; 1 0 mu M) reduced neutrophil adhesion. Superoxide dismutase (1,000 U/ml) had no effect. Pretreatment of HUVEC with 50 mu M tungsten also block ed xanthine-induced adherence. Adhesion was also inhibited by preincub ation with 100 U/ml heparin. Finally, anti-P-selectin antibody (PB1.3; 20 mu g/ml) attenuated adhesion. Our results indicate that xanthine m ay promote neutrophil-endothelial adhesion via a hydrogen peroxide- an d PAF-mediated P-selectin expression.