MONOCYTE CELL-SURFACE CD14 EXPRESSION AND SOLUBLE CD14 ANTIGEN IN HEMODIALYSIS - EVIDENCE FOR CHRONIC EXPOSURE TO LPS

Expression of CD14 on peripheral blood monocytes and serum levels of the 53 kD soluble CD14 antigen were investigated in patients with end-stage renal failure who were undergoing chronic hemodialysis (HD) with either cuprophane/hemophane (CU/HE) low-flux (LF) or polysulfone/polyamide (PS/PA) high-flux (HF) membranes. Baseline expression of CD14 was significantly lower in KD patients compared to uremic patients and normal controls. Patients using PS/PA membranes disclosed a further decreased CD14 expression than patients with CU/HE membranes. Specific fluorescence intensity for CD14 increased 15 minutes after the start of the dialysis session and was on average 22% higher after hemodialysis. The serum levels of sCD14 were elevated about 2.5-fold in HD patients compared to healthy controls (5.4 +/- 1.3 vs. 2.2 +/- 0.5 mg/liter, P < 0.0001) and were significantly higher compared to non-dialyzed patients with chronic renal failure (3.9 +/- 1.0 mg/liter, P < 0.001), After regular dialysis with high-flux membranes, soluble CD14 serum concentrations significantly increased (P < 0.001) compared to pre-dialysis levels. Values of soluble CD8 (54 kD) were elevated only 1.5-fold in HD patients relative to healthy controls, whereas serum levels of the low molecular weight soluble CD23 (20 kD) 12 and 19-fold in patients treated with HF-HD and LF-HD, reflecting the renal impairment and filtration through HF membranes. Thus, high sCD14 values in HD patients may stem from increased release of the up-regulated membrane antigen due to monocyte activation during hemodialysis treatment. Since the CD14 antigen is involved in LPS-induced monocyte activation, the influence of lipopolysaccharide on CD14 expression and sCD14 release was investigated in vitro. Addition of 1 ng/ml or 0.01 ng/ml LPS to whole blood significantly enhanced monocyte CD14 expression after 30 or 60 minutes of incubation. The release of soluble CD14 by cultured peripheral blood monocytes significantly increased in the presense of 0.01 ng/ml LPS during a five-day incubation experiment. Our results demonstrate an enhanced expression of CD14 by monocytes after HD and increased sCD14 serum levels possibly due to chronic exposure to trace amounts of endotoxins, as supported by in vitro experiments.