Purpose: Microaggregates have often been observed during hemodialysis and are clearly associated with complications of hemodialysis therapy. In this study, we aimed to clarify the effects of two polysulfone membranes, with different abilities to activate blood cells, on the formation of these microaggregates; we also investigated their molecular mechanisms. Methods: Human whole blood was circulated through a mini-module dialyzer using the membranes in vitro; platelet–neutrophil complexes in blood were determined by flow cytometry. Isolated human neutrophils were incubated with the membranes in plasma, in the presence or absence of platelets, followed by flow cytometric analysis of intracellular reactive oxygen species and cell-surface activated CD11b on neutrophils. Results: CX-U, a conventional polysulfone membrane with remarkable cell activation, induced the formation of platelet–neutrophil complexes; however, NV-U, a new hydrophilic polysulfone membrane with slight or no cell activation, did not cause complex formation. Moreover, CX-U-induced reactive oxygen species production and the increase in activated CD11b expression on neutrophils were enhanced by platelets. On the other hand, NV-U hardly affected neutrophil activation, regardless of whether platelets were present or not. The enhancement of CX-U-induced neutrophil activations by platelets was greatly inhibited by anti-CD62P antibody. Conclusion: The ability of polysulfone membranes to activate blood cells is closely related to platelet–neutrophil interaction. Therefore, a biocompatible membrane, like NV-U, can be expected to prevent microaggregate formation during hemodialysis and avoid subsequent cell activation.
Molecular Mechanisms of the Crosstalk Between Mitochondria and NADPH Oxidase Through Reactive Oxygen Species—Studies in White Blood Cells and in Animal Models
