Patey N, Lesavre P, Halbwachs-Mecarelli L, Noël L H
INSERM U90 and Department of Nephrology, Hôpital Necker, Paris, France.
J Pathol. 1996 Aug;179(4):414-20. doi: 10.1002/(SICI)1096-9896(199608)179:4<414::AID-PATH601>3.0.CO;2-J.
The expression of the intercellular adhesion molecule-1 (ICAM-1) and its ligand lymphocyte function associated antigen-1 (LFA-1 or alpha L), the vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1), and the cellular receptors for extracellular matrix, alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha V, beta 1, and beta 3 integrin subunits, was studied in 28 patients with crescentic glomerulonephritis (GN) related to several mechanisms: four patients with anti-glomerular basement membrane antibodies or anti-GBM disease; 16 with immune complex mediated GN; and eight with pauci-immune GN, associated with vasculitis in four cases. A three-step immunoperoxidase technique was used on sections obtained from frozen renal biopsies. At the initial stage of evolution of the lesions, all the cells of the crescents expressed the beta 1, beta 3, alpha 1, alpha 3, and alpha V subunits of integrins, ICAM-1, and VCAM-1, and some cells expressed the alpha 2, alpha 5, alpha 6, and alpha L subunits of integrins along the plasma membrane. At a later stage, when the crescents were fibrocellular, alpha 3 and alpha 1 subunit expression was polarized, localized mainly in front of the extracellular matrix. In fibrotic crescents, the alpha 2, alpha 5, alpha 6, and alpha L chains were no longer detected, and VCAM-1 and ICAM-1 expression was decreased. VCAM-1 and ELAM-1 appeared on endothelial cells of peritubular capillaries in relation to the appearance of infiltrating inflammatory cells. The results of this study show that several adhesion molecules were expressed on cells forming crescents and were modified during crescent evolution; that these molecules were up-regulated on endothelial cells in relation to the severity of the inflammatory response; and that whatever the mechanism of the glomerulonephritis, adhesion molecule expression was identical. It can be postulated that adhesion molecules play a role in crescentic glomerulonephritis. Better knowledge of these molecules in human glomerulonephritis may open the way to a new therapeutic approach.
研究了28例与多种机制相关的新月体性肾小球肾炎（GN）患者细胞间黏附分子-1（ICAM-1）及其配体淋巴细胞功能相关抗原-1（LFA-1或αL）、血管细胞黏附分子-1（VCAM-1）、内皮细胞白细胞黏附分子-1（ELAM-1）以及细胞外基质的细胞受体α1、α2、α3、α5、α6、αV、β1和β3整合素亚单位的表达情况。这些患者的发病机制包括：4例抗肾小球基底膜抗体或抗GBM病患者；16例免疫复合物介导的GN患者；8例寡免疫性GN患者，其中4例伴有血管炎。采用三步免疫过氧化物酶技术对取自冷冻肾活检组织的切片进行检测。在病变演变的初始阶段，新月体的所有细胞均表达整合素的β1、β3、α1、α3和αV亚单位、ICAM-1和VCAM-1，部分细胞沿质膜表达整合素的α2、α5、α6和αL亚单位。在后期，当新月体为纤维细胞性时，α3和α1亚单位的表达呈极化状态，主要定位于细胞外基质前方。在纤维化新月体中，不再检测到α2、α5、α6和αL链，且VCAM-1和ICAM-1的表达降低。随着浸润性炎性细胞的出现，VCAM-1和ELAM-1出现在肾小管周围毛细血管的内皮细胞上。本研究结果表明，几种黏附分子在形成新月体的细胞上表达，并在新月体演变过程中发生改变；这些分子在内皮细胞上的表达与炎症反应的严重程度相关上调；且无论肾小球肾炎的机制如何，黏附分子的表达均相同。可以推测黏附分子在新月体性肾小球肾炎中起作用。对人类肾小球肾炎中这些分子的深入了解可能为新的治疗方法开辟道路。
