Lehto T, Honkanen E, Teppo A M, Meri S
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Kidney Int. 1995 May;47(5):1403-11. doi: 10.1038/ki.1995.197.
Protectin (CD59) is a low molecular weight glycophosphoinositol-anchored inhibitor of the membrane attack complex of complement (MAC) that is present, for example, on the membranes of endothelial cells and on epithelial cells of glomeruli and distal tubuli. To examine for the possibility that CD59 becomes detached from cell surfaces following cell injury, this study evaluated renal excretion of CD59 in patients with idiopathic membranous glomerulonephritis (MGN; N = 21), diabetic nephropathy (DNP; N = 15) and in healthy control subjects (N = 13). CD59 in human urine was quantitated by a competitive solid-phase radioimmunoassay having approximately 13 kDa soluble urinary CD59 as a standard. Immunofluorescence microscopy demonstrated a decreased expression of CD59 in the glomeruli of MGN patients. Using a Triton X-114 phase separation method 91 to 97% of urinary CD59 was found to be in a soluble form without anchor-associated phospholipid. The mean (+/- SEM) level of urinary CD59 was 5.6 +/- 0.2 micrograms/ml in MGN patients, 3.7 +/- 0.4 micrograms/ml in healthy controls (P < 0.001) and 2.6 +/- 0.1 in DNP patients (P < 0.001). When related to urinary creatinine (UCr) the corresponding values were 11.9 +/- 5.6, 4.8 +/- 0.3 (P = 0.021) and 4.4 +/- 0.2 (P < 0.002), respectively. The amount of CD59 in urine correlated with the urinary excretion of soluble terminal complement complexes, SC5b-9 (r = 0.594, P < 0.006) in MGN patients. The excretion of CD59 also correlated with the excretion of the inflammatory mediator IL-1 beta (r = 0.671, P = 0.001) but not with TNF-alpha (r = 0.314, P = 0.178). No correlation of CD59 excretion was observed with duration of the disease level of proteinuria, serum albumin concentration or serum creatinine level. Based on these findings we speculate that the increased excretion of CD59 into urine in MGN patients is due to complement activation and inflammation induced shedding of CD59 from glomerular cells.
保护素（CD59）是一种低分子量的糖基磷脂酰肌醇锚定的补体膜攻击复合物（MAC）抑制剂，例如存在于内皮细胞膜以及肾小球和远端肾小管的上皮细胞膜上。为了研究细胞损伤后CD59是否会从细胞表面脱落，本研究评估了特发性膜性肾小球肾炎（MGN；n = 21）、糖尿病肾病（DNP；n = 15）患者及健康对照者（n = 13）尿中CD59的排泄情况。采用竞争性固相放射免疫分析法，以约13 kDa的可溶性尿CD59为标准，对人尿中的CD59进行定量。免疫荧光显微镜检查显示MGN患者肾小球中CD59表达降低。采用Triton X - 114相分离法发现，91%至97%的尿CD59为无锚定相关磷脂的可溶性形式。MGN患者尿CD59的平均（±SEM）水平为5.6±0.2μg/ml，健康对照者为3.7±0.4μg/ml（P < 0.001），DNP患者为2.6±0.1μg/ml（P < 0.001）。与尿肌酐（UCr）相关时，相应值分别为11.9±5.6、4.8±0.3（P = 0.021）和4.4±0.2（P < 0.002）。MGN患者尿中CD59的量与可溶性末端补体复合物SC5b - 9的尿排泄量相关（r = 0.594，P < 0.006）。CD59的排泄也与炎症介质IL - 1β的排泄相关（r = 0.671，P = 0.001），但与TNF - α无关（r = 0.314，P = 0.178）。未观察到CD59排泄与疾病持续时间、蛋白尿水平、血清白蛋白浓度或血清肌酐水平之间的相关性。基于这些发现，我们推测MGN患者尿中CD59排泄增加是由于补体激活和炎症诱导肾小球细胞上的CD59脱落所致。
