Biocompatibility of Polysulfone Hemodialysis Membranes and Its Mechanisms: Involvement of Fibrinogen and Its Integrin Receptors in Activation of Platelets and Neutrophils

: Activation of blood cells during hemodialysis is considered to be a significant determinant of biocompatibility of the hemodialysis membrane because it may affect patient health adversely through microvascular inflammation and oxidative stress. This study found very different cell activation among various polysulfone (PSf) hemodialysis membranes. For example, CX-U, a conventional PSf membrane, induced marked adhesion of platelets to its surface and increased surface expression of activated CD11b and production of reactive oxygen species (ROS) by neutrophils; while NV-U, a hydrophilic polymer-immobilized PSf membrane, caused little platelet adhesion and slight CD11b expression and ROS production by neutrophils. Analysis of the molecular mechanisms of the above phenomena on CX-U and NV-U indicated that anti-integrin GPIIb/IIIa antibody blocked platelet adhesion, and that the combination of anti-CD11b (integrin α subunit of Mac-1) and anti-integrin αvβ3 antibodies blocked ROS production by neutrophils. Plasma-derived fibrinogen, a major ligand of GPIIb/IIIa, Mac-1, and αvβ3 on membranes, was thus analyzed and found to be more adsorbed to CX-U than to NV-U. Moreover, comparison between five PSf membranes showed that the number of adherent platelets and neutrophil ROS production increased with increasing fibrinogen adsorption. These results suggested that fibrinogen, adsorbed on membranes, induced GPIIb/IIIa-mediated platelet activation and Mac-1/αvβ3-mediated neutrophil activation, depending on the amount of adsorption. In conclusion, the use of biocompatible membranes like NV-U, which show lower adsorption of fibrinogen, is expected to reduce hemodialysis-induced inflammation and oxidative stress by minimizing cell activation.