Segawa C, Wada T, Takaeda M, Furuichi K, Matsuda I, Hisada Y, Ohta S, Takasawa K, Takeda S, Kobayashi K, Yokoyama H
First Department of Internal Medicine, School of Medicine, Kanazawa University, Ishikawa, Japan.
Kidney Int. 1997 Oct;52(4):1054-63. doi: 10.1038/ki.1997.428.
To clarify the early involvement of cellular adhesion molecules in human glomerulonephritis, we investigated P-selectin and high endothelial venules' (HEVs) marker MECA-79 expression in kidney specimens by immunohistochemical and in situ hybridization analyses, and measured serum and urinary soluble P-selectin levels by enzyme-linked immunosorbent assay. In normal controls, P-selectin and MECA-79 expression were negative in glomeruli (N = 4), and serum soluble P-selectin levels were 114.3 +/- 36.8 ng/ml (mean +/- SEM, N = 12). Soluble P-selectin was not detectable in urine of all cases. In proliferative glomerulonephritis involving rapidly progressive glomerulonephritis (N = 6), IgA nephropathy (N = 26), lupus nephritis (N = 7) and acute glomerulonephritis (N = 2), both glomerular and interstitial P-selectin expression were up-regulated. Glomerular P-selectin expression correlated positively with local cellular accumulation, endocapillary proliferation and CD41b (platelet) staining. Interstitial P-selectin expression showed a positive correlation with the grade of local cellular infiltrates. P-selectin mRNA signals detected by in situ hybridization were only observed on capillary or venous endothelium in the interstitium, but not in glomeruli. In addition, MECA-79 was expressed on the plump endothelial cells at the cortico-medullary junction (outer medulla). Serum soluble P-selectin levels were significantly higher in patients with proliferative glomerulonephritis, especially in glomerular and interstitial P-selectin positive staining, and correlated with glomerular endocapillary proliferation. These observations suggested that P-selectin was associated with both glomerular and interstitial leukocyte accumulation in human glomerulonephritis, and might be expressed by two distinct mechanisms that are the activated platelets in glomeruli and the de novo expression in the interstitial lesions that correlated with MECA-79 expression as HEVs like vessels, and serum soluble P-selectin may be a useful marker for predicting in situ P-selectin expression associated with glomerular endocapillary proliferation in nephritis.
为阐明细胞黏附分子在人类肾小球肾炎中的早期参与情况，我们通过免疫组织化学和原位杂交分析研究了肾标本中P-选择素和高内皮微静脉（HEVs）标志物MECA-79的表达，并通过酶联免疫吸附测定法测量血清和尿液中可溶性P-选择素水平。在正常对照中，肾小球中P-选择素和MECA-79表达为阴性（N = 4），血清可溶性P-选择素水平为114.3±36.8 ng/ml（平均值±标准误，N = 12）。所有病例的尿液中均未检测到可溶性P-选择素。在包括急进性肾小球肾炎（N = 6）、IgA肾病（N = 26）、狼疮性肾炎（N = 7）和急性肾小球肾炎（N = 2）的增生性肾小球肾炎中，肾小球和间质P-选择素表达均上调。肾小球P-选择素表达与局部细胞聚集、毛细血管内增生和CD41b（血小板）染色呈正相关。间质P-选择素表达与局部细胞浸润程度呈正相关。原位杂交检测到的P-选择素mRNA信号仅在间质中的毛细血管或静脉内皮上观察到，而不在肾小球中。此外，MECA-79在皮质-髓质交界处（外髓）的丰满内皮细胞上表达。增生性肾小球肾炎患者血清可溶性P-选择素水平显著升高，尤其是在肾小球和间质P-选择素阳性染色时，且与肾小球毛细血管内增生相关。这些观察结果表明，P-选择素与人类肾小球肾炎中肾小球和间质白细胞聚集均相关，可能通过两种不同机制表达，即肾小球中活化的血小板和与MECA-79表达相关的间质病变中如HEVs样血管的从头表达，血清可溶性P-选择素可能是预测与肾炎中肾小球毛细血管内增生相关的原位P-选择素表达的有用标志物。
