Local macrophage proliferation correlates with increased renal M-CSF expression in human glomerulonephritis

Local macrophage proliferation correlates with increased renal M-CSF expression in human glomerulonephritis
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DOI:
10.1093/ndt/16.8.1638
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发表时间:
2001-08-01
影响因子:
6.1
通讯作者:
Atkins, RC
Atkins, RC
中科院分区:
医学1区
文献类型:
--
作者:
Isbel, NM;Nikolic-Paterson, DJ;Atkins, RC

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背景。巨噬细胞积聚是多种形式的肾小球肾炎的一个显着特征。在人类和实验性肾小球肾炎中已经描述了肾脏内巨噬细胞的局部增殖,并且可能在增强炎症反应中发挥重要作用。本研究探讨了局部巨噬细胞增殖与肾脏巨噬细胞集落刺激因子(M-CSF)表达之间的关系。方法。分别通过单次和双重免疫组织化学染色检查了总共 118 例患有广泛肾小球肾病的患者的肾活检中的 M-CSF 蛋白和巨噬细胞增殖(KP1 + PCNA + 细胞)。结果。组织学正常肾脏的薄膜病 (TMD) 活检显示 33% 的皮质小管表达 M-CSF 蛋白,而肾小球 M-CSF 表达仅限于常驻巨噬细胞和一些足细胞。在增殖型肾小球肾炎中,肾小球 M-CSF 表达显着增加,浸润巨噬细胞、足细胞和一些系膜细胞的 M-CSF 染色。 M-CSF 强表达的节段区域,尤其是新月体,与 KP1+PCNA+ 增殖巨噬细胞共定位。大多数类型的肾小球肾炎中肾小管 M-CSF 表达也有所增加。肾小管 M-CSF 染色在肾小管损伤区域最强,并与 KP1 + 巨噬细胞(包括 KP1+PCNA+ 增殖巨噬细胞)共定位。许多间质巨噬细胞和α-平滑肌肌动蛋白阳性肌成纤维细胞显示出强烈的M-CSF染色。统计分析显示肾小球和肾小管间质中 M-CSF 表达与局部巨噬细胞增殖之间存在高度显着相关性。肾小球和肾小管 M-CSF 表达与肾功能障碍显着相关。结论。肾小球和肾小管间质 M-CSF 表达在人肾小球肾炎中上调,在增殖性疾病中最为突出。这与局部巨噬细胞增殖相关。表明肾脏 M-CSF 产生的增加在调节人肾小球肾炎局部巨噬细胞增殖中发挥重要作用。
Background. Macrophage accumulation is a prominent feature in many forms of glomerulonephritis. Local proliferation of macrophages within the kidney has been described in human and experimental glomerulonephritis and may have an important role in augmenting the inflammatory response. The current study examined the relationship between local macrophage proliferation and renal expression of macrophage colony-stimulating factor (M-CSF).Methods. A total of 118 renal biopsies of patients with a wide range of glomerulonephridities were examined for M-CSF protein and macrophage proliferation (KP1 + PCNA +cells) by single and double immunohistochemistry staining, respectively.Results. Biopsies of thin membrane disease (TMD) with histologically normal kidney showed M-CSF protein expression by 33% of cortical tubules, while glomerular M-CSF expression was limited to resident macrophages and some podocytes. Glomerular M-CSF expression increased significantly in proliferative forms of glomerulonephritis, with M-CSF staining of infiltrating macrophages, podocytes and some mesangial cells. Segmental areas of strong M-CSF expression, particularly in crescents, co-localized with KP1+PCNA+ proliferating macrophages. There was also an increase in tubular M-CSF expression in most types of glomerulonephritis. Tubular M-CSF staining was strongest in areas of tubular damage and co-localized with KP1 + macrophages, including KP1+PCNA+ proliferating macrophages. Many interstitial macrophages and a-smooth muscle actin-positive myofibroblasts showed strong M-CSF staining. Statistical analysis showed a highly significant correlation between M-CSF expression and local macrophage proliferation in both the glomerulus and tubulointerstitium. Glomerular and tubular M-CSF expression gave a significant correlation with renal dysfunction.Conclusions. Glomerular and tubulointerstitial M-CSF expression is up-regulated in human glomerulonephritis, being most prominent in proliferative forms of disease. This correlated with local macrophage proliferation. suggesting that increased renal M-CSF production plays an important role in regulating local macrophage proliferation in human glomerulonephritis.