Endothelial adhesion molecules in glomerular lesions: Association with their severity and diversity in lupus models
Endothelial adhesion molecules in glomerular lesions: Association with their severity and diversity in lupus models
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DOI：
10.1111/j.1523-1755.2004.00537.x
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发表时间：
2004-04-01
影响因子：
19.6
通讯作者：
Nose, M
中科院分区：
文献类型：
--
作者：
Nakatani, K;Fujii, H;Nose, M
背景为了阐明肾小球血管内皮细胞粘附分子是否与狼疮性肾炎肾小球病变的严重性和多样性有关，分析了其在狼疮模型中的表达。采用激光捕获显微切割技术，结合逆转录-聚合酶链反应（RT-PCR）技术，研究了不同病理分级的MRL/MpJ-lpr/lpr（MRL/lpr）狼疮小鼠肾小球E-选择素、P-选择素和血管细胞粘附分子-1（VCAM-1）的表达水平。分析了用2B11.3和7B6.8克隆注射的SCID小鼠中的肾小球病变，2B11.3和7B6.8克隆来源于MRL/lpr小鼠并分别诱导毛细血管内增殖和线环型肾小球病变。为研究可溶性E-选择素（sE-selectin）对肾小球病变的影响，通过转染编码sE-选择素的cDNA制备了分泌sE-选择素的L细胞，并注射到SCID小鼠体内。在MRL/lpr小鼠的肾小球表现出这些粘附分子的表达增加，对应于肾小球病变的严重程度。2B11.3克隆诱导的SCID小鼠毛细血管内增殖型病变显示粘附分子，尤其是E-选择素和P-选择素的表达显著增加，但7B6.8克隆诱导的线环型病变仅表达VCAM-1。由2B11.3克隆诱导的毛细血管内增殖型病变的形成被显著阻止，这与由转染的L细胞产生的血清sE-选择素水平升高有关。狼疮性肾炎组织病理学的严重性和多样性与肾小球血管内皮粘附分子的表达部分相关。
Background. To clarify whether vascular endothelial adhesion molecules in glomeruli might contribute to the severity and diversity of glomerular lesions in lupus nephritis, their expression in lupus models was analyzed.Methods. The expression levels of E- and P-selectin and vascular cell adhesion molecule-1 (VCAM-1) in glomeruli of different histopathologic grades of MRL/MpJ-lpr/lpr (MRL/lpr) lupus mice was studied using laser-capture microdissection of the glomeruli, followed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. The glomerular lesions in SCID mice injected with the 2B11.3 and 7B6.8 clones, which are derived from an MRL/lpr mouse and induce endocapillary proliferative and wire loop type of glomerular lesions, respectively, were analyzed. To investigate the effect of a soluble form of E- selectin (sE-selectin) on the development of glomerular lesions, sE-selectin-producing L cells were prepared by transfection of the cDNA encoding sE-selectin and injected into SCID mice.Results. The glomeruli in MRL/lpr mice showed increased expression of these adhesion molecules, corresponding to the severity of the glomerular lesions. The endocapillary proliferative type lesions in SCID mice induced by the 2B11.3 clone showed significantly increased expression of the adhesion molecules, especially E- selectin and P-selectin, but the wire loop type lesion induced by the 7B6.8 clone expressed only VCAM-1. Formation of the endocapillary proliferative type lesions induced by the 2B11.3 clone was markedly prevented in association with elevation of the serum level of sE-selectin produced by the tansfected L cells.Conclusion. The severity and diversity of the histopathology of lupus nephritis are partially associated with the expression of vascular endothelial adhesion molecules in glomeruli.