The sialoadhesin (CD169) expressing a macrophage subset in human proliferative glomerulonephritis
The sialoadhesin (CD169) expressing a macrophage subset in human proliferative glomerulonephritis
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DOI：
10.1093/ndt/gfi105
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发表时间：
2005-12-01
影响因子：
6.1
通讯作者：
Uchiyama, M
中科院分区：
文献类型：
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作者：
Ikezumi, Y;Suzuki, T;Uchiyama, M
背景唾液酸粘附素（Sn; CD 169）是一种凝集素样受体，其表达仅限于组织和炎性巨噬细胞的亚群。我们以前已经确定的积累锡+巨噬细胞作为一个重要的标志物的疾病进展与缓解大鼠系膜增生性肾炎。本研究探讨Sn+巨噬细胞在人增生性肾小球肾炎中的意义。通过免疫荧光对来自正常成人肾脏（n = 4）和小儿肾病（n 40）的冷冻肾脏切片的总巨噬细胞（CD 68+细胞）、Sn+巨噬细胞、CD 3 + T细胞和I型胶原进行染色。对白细胞浸润和肾小球病变及间质损害的严重程度进行评分。对27例患者进行了第二方案活检，并获得了临床和活检基础数据。Sn+巨噬细胞在正常成人肾脏和薄基底膜病（n = 4）肾小球中不存在，但在9例紫癜性肾炎中的4例、17例伊加肾病中的7例、5例膜增生性肾炎中的5例和5例狼疮性肾炎中检测到。Sn+巨噬细胞定位于局灶性肾小球和间质损伤区域。双色免疫染色证实Sn+细胞是总CD 68+巨噬细胞的一个子集。肾小球Sn+巨噬细胞数量与蛋白尿和肾小球病变程度相关（r = 0.44，P = 0.0045; r = 0.82，P < 0.0001;而间质Sn+巨噬细胞与蛋白尿和间质损害程度相关（r分别为0.59，P < 0.0001和0.75，P < 0.0001）。联合免疫组化染色显示，间质Sn+巨噬细胞和CD 3 + T细胞共定位于肾小管间质损伤的区域，I型胶原沉积增加。间质Sn+巨噬细胞数与CD 3 + T细胞数呈显著相关（r = 0.74，P < 0.0001）。大多数患者对2年的糖皮质激素治疗有反应，蛋白尿和肾小球病变减少，这与肾小球Sn+巨噬细胞数量减少相关。本研究已将Sn+细胞鉴定为巨噬细胞亚群，其在肾脏中的积累与蛋白尿和组织学损伤相关。这些结果，以及最近的动物研究结果表明，Sn+巨噬细胞可能在进行性肾脏疾病中发挥重要作用。
Background. Sialoadhesin ( Sn; CD169) is a lectin-like receptor whose expression is restricted to subsets of tissue and inflammatory macrophages. We have previously identified accumulation of Sn+ macrophages as an important marker of disease progression versus remission in rat mesangial proliferative nephritis. The current study examined the significance of Sn+ macrophages in human proliferative glomerulonephritis.Methods. Frozen kidney sections from normal adult human kidney ( n = 4) and pediatric nephropathy ( n 40) were stained for total macrophages ( CD68+ cells), Sn+ macrophages, CD3+ T-cells and collagen type I by immunofluorescence. Leukocyte infiltration and the severity of glomerular lesions and interstitial damage were scored. A second protocol biopsy was performed in 27 cases and clinical and biopsy-based data obtained.Results. Sn+ macrophages were absent from glomeruli in normal adult human kidney and in thin basement membrane disease ( n = 4), but were detected in 4 of 9 cases of purpura nephritis; 7 of 17 IgA nephropathy; 5 of 5 membranoproliferative glomerulonephritis, and 5 of 5 lupus nephritis. Sn+ macrophages were localized in areas of focal glomerular and interstitial damage. Two-colour immunostaining confirmed that Sn+ cells are a subset of total CD68+ macrophages. The number of glomerular Sn+ macrophages correlated with the degree of proteinuria and glomerular lesions ( r = 0.44, P = 0.0045 and r = 0.82, P < 0.0001; respectively), while interstitial Sn+ macrophages correlated with the degree of proteinuria and interstitial damage ( r = 0.59, P < 0.0001 and r = 0.75, P < 0.0001; respectively). Combined immunostaining revealed that interstitial Sn+ macrophages and CD3+ T-cells co-localized in areas of tubulointerstitial damage with increased type I collagen deposition. There was significant correlation between the number of interstitial Sn+ macrophages and CD3+ T-cells ( r = 0.74, P < 0.0001). Most patients responded to a 2 year period of glucocorticoid therapy with a reduction in proteinuria and glomerular lesions and this correlated with the reduction in the number of glomerular Sn+ macrophages.Conclusion. This study has identified Sn+ cells as a macrophage subset whose accumulation in the kidney correlates with proteinuria and histologic damage. These results, together with recent findings from animal studies, suggest that Sn+ macrophages may play an important role in progressive renal disease.