Mizutani M, Yuzawa Y, Maruyama I, Sakamoto N, Matsuo S
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Lab Invest. 1993 Aug;69(2):193-202.
Thrombomodulin (TM), a glycoprotein expressed on the surface of endothelial cells, transforms protein C into a potent anticoagulant by binding thrombin. TM may be an important regulator of intraglomerular coagulation because functional TM activity was demonstrated in glomeruli isolated from normal human and rat kidneys. The role of TM in glomerulonephritis is unknown.
Sections from 4 normal human kidneys and from kidneys of 100 patients with various forms of glomerulonephritis were studied by light and transmission electron microscopy, and by light and electron immunohistochemical techniques using polyclonal antibodies to recombinant human TM, and monoclonal antibodies to the membrane attack complex of the complement system. The expression of TM was graded from 0 to 4 according to the intensity and extent of the distribution, and the results were compared with the clinicopathologic findings.
In normal glomeruli and in glomeruli with minimal abnormalities, a small amount of TM was localized at the vascular pole only (grade 0-1). In membranoproliferative glomerulonephritis and lupus glomerulonephritis, the amount of TM found on the plasma membrane of endothelial cells was significantly increased (grades 2 to 4). The expression of TM was directly correlated with proteinuria (p < 0.001), glomerular hypercellularity (p < 0.01), and number of subendothelial immune deposits (p < 0.01). In contrast, in other forms of glomerular diseases, TM was not increased and no correlation was found with the clinicopathologic parameters.
In membranoproliferative glomerulonephritis and lupus glomerulonephritis, the amount of TM expressed by the plasma membranes of glomerular endothelial cells is increased, and this finding is a marker of disease activity. The significance of an increased expression of an endothelial anticoagulant glycoprotein in diseases characterized by pathologic intraglomerular coagulation is unknown, and requires further studies.
血栓调节蛋白（TM）是一种在内皮细胞表面表达的糖蛋白，通过结合凝血酶将蛋白C转化为一种强效抗凝剂。TM可能是肾小球内凝血的重要调节因子，因为在从正常人和大鼠肾脏分离的肾小球中已证实存在功能性TM活性。TM在肾小球肾炎中的作用尚不清楚。
对4例正常人类肾脏以及100例患有各种形式肾小球肾炎患者的肾脏切片进行光镜和透射电镜检查，并采用针对重组人TM的多克隆抗体以及针对补体系统膜攻击复合物的单克隆抗体进行光镜和电镜免疫组化技术研究。根据分布的强度和范围将TM的表达分为0至4级，并将结果与临床病理结果进行比较。
在正常肾小球和仅有轻微异常的肾小球中，少量TM仅定位于血管极（0-1级）。在膜增生性肾小球肾炎和狼疮性肾小球肾炎中，在内皮细胞质膜上发现的TM量显著增加（2至4级）。TM的表达与蛋白尿（p < 0.001）、肾小球细胞增多（p < 0.01）以及内皮下免疫沉积物数量（p < 0.01）直接相关。相比之下，在其他形式的肾小球疾病中，TM未增加，且与临床病理参数无相关性。
在膜增生性肾小球肾炎和狼疮性肾小球肾炎中，肾小球内皮细胞质膜表达的TM量增加，这一发现是疾病活动的标志物。在内皮抗凝糖蛋白表达增加在以病理性肾小球内凝血为特征的疾病中的意义尚不清楚，需要进一步研究。
