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 t he 53 kD soluble CD14 antigen were investigated in patients with end-s tage renal failure who were undergoing chronic hemodialysis (HD) with either cuprophane/hemophane (CU/HE) low-flux (LF) or polysulfone/polya mide (PS/PA) high-flux (HF) membranes. Baseline expression of CD14 was significantly lower in KD patients compared to uremic patients and no rmal controls. Patients using PS/PA membranes disclosed a further decr eased CD14 expression than patients with CU/HE membranes. Specific flu orescence intensity for CD14 increased 15 minutes after the start of t he 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 patie nts with chronic renal failure (3.9 +/- 1.0 mg/liter, P < 0.001), Afte r regular dialysis with high-flux membranes, soluble CD14 serum concen trations significantly increased (P < 0.001) compared to pre-dialysis levels. Values of soluble CD8 (54 kD) were elevated only 1.5-fold in H D patients relative to healthy controls, whereas serum levels of the l ow molecular weight soluble CD23 (20 kD) 12 and 19-fold in patients tr eated with HF-HD and LF-HD, reflecting the renal impairment and filtra tion through HF membranes. Thus, high sCD14 values in HD patients may stem from increased release of the up-regulated membrane antigen due t o monocyte activation during hemodialysis treatment. Since the CD14 an tigen is involved in LPS-induced monocyte activation, the influence of lipopolysaccharide on CD14 expression and sCD14 release was investiga ted in vitro. Addition of 1 ng/ml or 0.01 ng/ml LPS to whole blood sig nificantly 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 du ring a five-day incubation experiment. Our results demonstrate an enha nced expression of CD14 by monocytes after HD and increased sCD14 seru m levels possibly due to chronic exposure to trace amounts of endotoxi ns, as supported by in vitro experiments.