Morita H, Shinzato T, Isobe K I, Kitani K, Kimata K, Maeda K
Department of Internal Medicine, The Branch Hospital of Nagoya University, School of Medicine, Japan.
Virchows Arch. 1999 Feb;434(2):145-51. doi: 10.1007/s004280050318.
Crescentic glomerulonephritis leads to a rapid loss of renal function. Although glomerular crescents are rich in extracellular matrix (ECM), the composition and genesis of the ECM are incompletely understood. Heparan sulfate (HS) is a major ECM molecule and has polymeric structure of great variability. Recent findings that alterations in HS epitopes are associated with renal pathology prompted us to hypothesize that specific HS epitopes might be expressed in the evolution of crescents. We reviewed clinical records of 724 patients who underwent renal biopsy and found 21 patients with rapidly progressive glomerulonephritis. Immunohistochemistry was performed using monoclonal antibodies (mAbs) against well-defined HS epitopes. One mAb was directed against unsaturated uronic acid residues generated during the selective removal of HS by heparitinase (a), and a further two different mAbs against N-sulfate-enriched and O-sulfate-poor portions of HS (b). Results showed that mAb (a) reacted to ECM of normal, sclerosed and crescentic glomeruli and that mAbs (b) reacted strongly to ECM of fibrocellular crescents but not to fibrous crescents, the periglomerular areas and noncrescentic intraglomerular areas. We concluded there are regional differences in HS epitope expression, although HS are ubiquitous components of glomerular ECM. N-sulfate-enriched and O-sulfate-poor portions of HS might play a role in crescent formation.
新月体性肾小球肾炎会导致肾功能迅速丧失。尽管肾小球新月体富含细胞外基质（ECM），但其细胞外基质的组成和成因尚未完全明确。硫酸乙酰肝素（HS）是一种主要的细胞外基质分子，具有高度可变的聚合结构。最近有研究发现，硫酸乙酰肝素表位的改变与肾脏病理相关，这促使我们推测，特定的硫酸乙酰肝素表位可能在新月体的演变过程中表达。我们回顾了724例接受肾活检患者的临床记录，发现其中21例患有快速进展性肾小球肾炎。使用针对明确的硫酸乙酰肝素表位的单克隆抗体（mAb）进行免疫组织化学检测。一种单克隆抗体针对在肝素酶选择性去除硫酸乙酰肝素过程中产生的不饱和糖醛酸残基（a），另外两种不同的单克隆抗体针对硫酸乙酰肝素富含N-硫酸酯且缺乏O-硫酸酯的部分（b）。结果显示，单克隆抗体（a）与正常、硬化和新月体性肾小球的细胞外基质发生反应，而单克隆抗体（b）对纤维细胞性新月体的细胞外基质反应强烈，但对纤维性新月体、肾小球周围区域和非新月体性肾小球内区域无反应。我们得出结论，尽管硫酸乙酰肝素是肾小球细胞外基质的普遍组成成分，但硫酸乙酰肝素表位表达存在区域差异。硫酸乙酰肝素富含N-硫酸酯且缺乏O-硫酸酯的部分可能在新月体形成中发挥作用。
