Abe K, Miyazaki M, Koji T, Furusu A, Ozono Y, Harada T, Sakai H, Nakane P K, Kohno S
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Kidney Int. 1998 Jul;54(1):120-30. doi: 10.1046/j.1523-1755.1998.00961.x.
Decay accelerating factor (DAF), a product of mesangial cells in vitro, is expressed on the surface of cells and is a candidate for the focal suppression of complement activation. It is not clear at present whether the levels of expression of DAF and intrarenal C3 synthesis correlate with the level of tissue injury.
Immunohistochemistry for DAF and C3 and nonradioactive in situ hybridization with digoxigenin-labeled oligonucleotide probe for DAF and C3 mRNA were performed in 22 tissue samples of kidneys from patients with IgA nephropathy (IgAN), 6 with membranous nephropathy (MN), 6 with lupus nephritis (LN), and five normal kidneys.
In the normal kidney, DAF was confined to the juxtaglomerular apparatus and little or no C3 was detected; however, a few glomerular cells were positive for DAF mRNA but no C3 mRNA positive cells were detected. In diseased kidneys, DAF and C3 as well as their mRNAs were detected in mesangial cells, tubular cells and infiltrating cells. Glomerular epithelial cells and Bowman's capsule cells contained little or no DAF and C3 but were positive for their mRNAs. The mean percentages of mesangial cells positive for DAF and C3 mRNAs were 49.3 +/- 11.5% and 50.7 +/- 10.3% in IgAN, and 17.0 +/- 6.3% and 19.4 +/- 9.0% in MN, respectively. The percentage of mesangial cells positive for DAF and C3 mRNAs among intraglomerular cells correlated positively with the degree of mesangial proliferation and glomerular sclerosis in IgAN. In contrast, in LN the percentage of glomerular cells positive for DAF mRNA correlated negatively with the degree of glomerular injury, while the percentage of cells positive for C3 mRNA did not change with the progression of the disease. The ratio of C3 mRNA/DAF mRNA of glomerular cells correlated with the degree of glomerular injury in both IgAN and LN. In the tubulointerstitium, the percentage of cells expressing mRNA, and C3 mRNA/DAF mRNA radio correlated with the degree of tubular atrophy and interstitial broadening in both IgAN and LN.
We conclude that DAF and C3 mRNAs are synthesized in human diseased kidneys, and that a balance between locally synthesized DAF and C3 may be important in the progression of glomerulonephritis.
衰变加速因子（DAF）是体外系膜细胞的产物，表达于细胞表面，是补体激活局部抑制的候选因子。目前尚不清楚DAF的表达水平和肾内C3合成是否与组织损伤程度相关。
对22例IgA肾病（IgAN）患者、6例膜性肾病（MN）患者、6例狼疮性肾炎（LN）患者的肾组织样本以及5例正常肾脏进行DAF和C3的免疫组化检测，并用地高辛标记的寡核苷酸探针进行DAF和C3 mRNA的非放射性原位杂交。
在正常肾脏中，DAF局限于肾小球旁器，几乎未检测到C3；然而，少数肾小球细胞DAF mRNA呈阳性，但未检测到C3 mRNA阳性细胞。在患病肾脏中，系膜细胞、肾小管细胞和浸润细胞中可检测到DAF和C3及其mRNA。肾小球上皮细胞和鲍曼囊细胞几乎不含有DAF和C3，但它们的mRNA呈阳性。IgAN中系膜细胞DAF和C3 mRNA阳性的平均百分比分别为49.3±11.5%和50.7±10.3%，MN中分别为17.0±6.3%和19.4±9.0%。IgAN中肾小球内DAF和C3 mRNA阳性的系膜细胞百分比与系膜增生和肾小球硬化程度呈正相关。相反，在LN中，DAF mRNA阳性的肾小球细胞百分比与肾小球损伤程度呈负相关，而C3 mRNA阳性细胞百分比不随疾病进展而变化。肾小球细胞C3 mRNA/DAF mRNA比值在IgAN和LN中均与肾小球损伤程度相关。在肾小管间质中，IgAN和LN中表达mRNA的细胞百分比以及C3 mRNA/DAF mRNA比值与肾小管萎缩和间质增宽程度相关。
我们得出结论，DAF和C3 mRNA在人类患病肾脏中合成，局部合成的DAF和C3之间的平衡可能在肾小球肾炎进展中起重要作用。
