Nockher W A, Scherberich J E
Department of Internal Medicine IV, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
Kidney Int. 1995 Nov;48(5):1469-76. doi: 10.1038/ki.1995.436.
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 HD 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 presence 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.
对正在接受使用铜仿膜/血仿膜（CU/HE）低通量（LF）或聚砜/聚酰胺（PS/PA）高通量（HF）膜进行慢性血液透析（HD）的终末期肾衰竭患者，研究了外周血单核细胞上CD14的表达及53 kD可溶性CD14抗原的血清水平。与尿毒症患者和正常对照相比，HD患者中CD14的基线表达显著降低。使用PS/PA膜的患者比使用CU/HE膜的患者表现出进一步降低的CD14表达。透析开始15分钟后，CD14的特异性荧光强度增加，血液透析后平均高出22%。与健康对照相比，HD患者的sCD14血清水平升高约2.5倍（5.4±1.3对2.2±0.5 mg/升，P<0.0001），与未透析的慢性肾衰竭患者相比也显著更高（3.9±1.0 mg/升，P<0.001）。用高通量膜定期透析后，可溶性CD14血清浓度与透析前水平相比显著增加（P<0.001）。HD患者中可溶性CD8（54 kD）的值相对于健康对照仅升高1.5倍，而在接受HF-HD和LF-HD治疗的患者中，低分子量可溶性CD23（20 kD）的血清水平分别升高12倍和19倍，这反映了肾功能损害以及通过HF膜的滤过情况。因此，HD患者中高sCD14值可能源于血液透析治疗期间单核细胞激活导致上调的膜抗原释放增加。由于CD14抗原参与脂多糖诱导的单核细胞激活，因此在体外研究了脂多糖对CD14表达和sCD14释放的影响。向全血中添加1 ng/ml或0.01 ng/ml脂多糖，孵育30或60分钟后显著增强单核细胞CD14表达。在为期五天的孵育实验中，在存在0.01 ng/ml脂多糖的情况下，培养的外周血单核细胞释放的可溶性CD14显著增加。我们的结果表明，血液透析后单核细胞中CD14表达增强，sCD14血清水平升高，这可能是由于长期暴露于痕量内毒素所致，体外实验也支持这一点。
