Preventive Effect of α-Tocopherol and Glycyrrhizin against Platelet-Neutrophil Complex Formation Induced by Hemodialysis Membranes

Abstract

Background The intradialytic activation of leukocytes is a major cause of hemodialysis (HD)-associated complications. Contact between blood and HD membranes frequently induces the formation of microaggregates composed of activated platelets and leukocytes, causing leukocyte activation that includes the generation of reactive oxygen species (ROS). This complex formation is mediated primarily by the interaction between P-selectin on activated platelets and its counter-ligands on leukocytes. Objective We examined the preventive effects of α-tocopherol and glycyrrhizin in vitro against platelet-neutrophil microaggregate formation and neutrophil ROS production induced by HD membranes. Methods and Results Microaggregate formation induced by the incubation of heparinized whole blood with polysulfone (PS) HD membranes was effectively inhibited by α-tocopherol and glycyrrhizin. α-Tocopherol, but not glycyrrhizin, was found to inhibit PS membrane-induced P-selectin expression on the platelet surface; however, glycyrrhizin did inhibit both the formation of neutrophil-platelet microaggregates induced by adenosine diphosphate (ADP) and the adhesion of HL60 leukemic cells to P-selectin-expressing Chinese hamster ovary (CHO) cells, suggesting that glycyrrhizin acts as a competitive inhibitor of P-selectin-mediated cell adhesion. Finally, these compounds almost completely abrogated PS membrane-induced and platelet-dependent ROS production by neutrophils. Conclusions These results suggest that α-tocopherol and glycyrrhizin may function as preventive agents of HD-associated leukocyte activation though the modulation of platelet-leukocyte interaction.