A novel mechanism of nephron loss in a murine model of crescentic glomerulonephritis
A novel mechanism of nephron loss in a murine model of crescentic glomerulonephritis
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DOI：
10.1046/j.1523-1755.2003.00782.x
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发表时间：
2003-02-01
影响因子：
19.6
通讯作者：
Besse-Eschmann, V
中科院分区：
文献类型：
--
作者：
Le Hir, M;Besse-Eschmann, V
背景肾单位丢失是肾小球疾病中肾功能衰竭的主要决定因素。流行的概念强调过滤蛋白质的毒性和/或间质炎症在肾小管变性中的作用。然而，这一概念是否与肾单位丢失的实际组织病理学特征相一致还没有具体研究。我们研究了小鼠新月体肾小球肾炎肾小管变性的形态学方面。静脉注射抗肾小球基底膜抗血清诱发致敏小鼠肾小球肾炎。通过灌注固定肾脏，并通过光镜和电子显微镜以及化学发光法进行检查。肾小管变性始于近端小管细胞萎缩。细胞新月体阻塞最初的近端小管后出现营养不良。而细胞间粘附分子-1（ICAM-1）的诱导是弥漫性的肾小球肾炎小鼠，CD 44和血管细胞粘附分子-1（VCAM-1）的表达似乎仅限于退化的肾小管。间质性炎症发生在变性小管附近。仅在肾小管变性的晚期才观察到肾小管本身的炎性浸润。与先前描述的局灶节段性肾小球硬化相似，新月体肾小球肾炎中的肾单位丢失可由肾小球病变进展至近端小管开始。间质性炎症可能是肾小管变性的结果而不是原因。
Background. Nephron loss is a major determinant of renal failure in glomerular diseases. The prevalent concept stresses the role of the toxicity of filtered proteins and/or of interstitial inflammation in tubular degeneration. However, whether that concept is compatible with the actual histopathological features of nephron loss has not been investigated specifically.Methods. We investigated the morphological aspects of tubular degeneration in crescentic glomerulonephritis in mice. Glomerulonephritis was induced by intravenous injection of anti-glomerular basement membrane antiserum in presensitized mice. Kidneys were fixed by perfusion and examined by light- and electron microscopy and by immunohistochemistry.Results. Tubular degeneration started with cellular hypotrophy in the proximal tubule. Hypotrophy appeared to follow obstruction of the initial proximal tubule by a cellular crescent. Whereas induction of intercellular adhesion molecule-1 (ICAM-1) was diffuse in glomerulonephritic mice, expression of CD44 and vascular cell adhesion molecule-1 (VCAM-1) appeared to be restricted to degenerating tubules. Interstitial inflammation developed in the vicinity of degenerating tubules. Inflammatory infiltration of tubules themselves was observed only in late stages of tubular degeneration.Conclusion. In a similar manner as described earlier for focal segmental glomerulosclerosis, in crescentic glomerulonephritis nephron loss can be initiated by the progression of a glomerular lesion into the proximal tubule. Interstitial inflammation might be rather a consequence than the cause of tubular degeneration.