Increased expression of the C3b receptor by neutrophils and complement activation during haemodialysis

Abstract

Activation of complement and the relative number of C3b receptors expressed by neutrophils was assessed in patients undergoing haemodialysis with new and reused cellulosic membranes, and with polymethylmethacrylate (PMMA) membranes. Activation of complement was assessed by radioimmunoassay of plasma C3adesArg, and neutrophil C3b receptors were measured by fluorescent flow cytometry of cells indirectly stained with F(ab')2 anti-C3b receptor. During first use of cellulosic dialysis membranes by four patients, the mean expression of C3b receptors by neutrophils in blood taken from the afferent line of the extra-corporeal system after 10, 20, 60 and 120 min of dialysis increased to 127, 189, 255 and 296%, respectively. The mean plasma C3adesArg concentrations in the corresponding samples of blood were 225, 320, 236 and 160% of the pre-dialysis levels. During third and fifth use of the same membranes by these patients, the mean C3b receptor expression by neutrophils did not exceed 150% of the predialysis determination, and correspondingly minimal increases in plasma C3adesArg were observed. Analysis of blood taken simultaneously from the afferent and efferent lines of the first use cellulosic dialysis system indicated that the increase in C3b receptor expression by neutrophils and generation of C3adesArg occurred when blood came in contact with the dialysis membrane. Haemodialysis of four additional patients with the non-complement activating PMMA membrane caused only modest or no increases in neutrophil C3b receptors. Thus, complement activation in vivo is associated with up-regulation of neutrophilic C3b receptors, indicating that this cellular response previously described only in model, in vitro systems, is a physiological mechanism by which this cell can augment its capacity for responding to C3b opsonized material.