Platelet activation through interaction with hemodialysis membranes induces neutrophils to produce reactive oxygen species

The intradialytic activation of leukocytes is one of the major causes of hemodialysis-associated complications. During hemodialysis, the formation of microaggregates consisting of platelets and neutrophils has been observed to accompany the production of reactive oxygen species (ROS) by leukocytes. In this study, we investigated the interaction of platelets and neutrophils with hemodialysis membranes in vitro to elucidate the mechanism underlying microaggregate formation and its relevance to leukocyte activation. The production of ROS in neutrophils was induced by the coincubation of neutrophils with polysulfone (PS) membranes, and was increased when platelets were present in the neutrophil suspension. Neutrophils that were incubated with polymethylmethacrylate (PMMA) membranes in the presence of platelets also produced significant levels of ROS, suggesting that the presence of platelets augmented ROS production in neutrophils. Platelets adhered more firmly to hydrophobic membranes such as PS and PMMA membranes than to hydrophilic membranes, such as those composed of regenerated cellulose (RC) or ethylene vinylalcohol copolymer (EVAL). The adhesion of platelets to dialysis membranes composed of different materials was correlated with those membranes' ability to induce platelet activation as assessed by the cell surface expression of P-selectin. Moreover, coincubation of neutrophils with platelets that had been treated with hydrophobic membranes induced a higher level of superoxide anion relative to those treated with hydrophilic membranes in association with the P-selectin-mediated microaggregate formation. These results suggest that platelets activated through interaction with hemodialysis membranes stimulate neutrophils to produce ROS via P-selectin-mediated adhesion, and that this property of adhesion to platelets is critical for the biocompatibility of hemodialysis membranes.