VASCULAR CELL-ADHESION MOLECULE-1 (VCAM-1) EXPRESSION IN MURINE LUPUS NEPHRITIS
VASCULAR CELL-ADHESION MOLECULE-1 (VCAM-1) EXPRESSION IN MURINE LUPUS NEPHRITIS
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DOI：
10.1038/ki.1992.367
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发表时间：
1992-10-01
影响因子：
19.6
通讯作者：
SNYDER, TL
中科院分区：
文献类型：
--
作者：
WUTHRICH, RP;SNYDER, TL
血管细胞粘附分子-1 (VCAM-1) 是一种细胞表面蛋白，通过与白细胞上的 β-1-整合素配体极晚期抗原-4 (VLA-4) 结合来介导炎症细胞与靶细胞的粘附。在狼疮肾炎小鼠模型（自身免疫 MRL/lpr 小鼠）中研究了 VCAM-1 的表达。与正常小鼠相比，MRL/lpr 肾脏不仅在内皮细胞中，而且在皮质小管和肾小球中也显示出 VCAM-1 表达增加。在肾病 MRL/lpr 小鼠的肾脏中检测到稳态 VCAM-1 mRNA 水平增加（约 3 kB）。两个额外的转录本（大约 2 kB 和大约 1.8 kB）存在于自身免疫 MRL/lpr 中，但不存在于正常小鼠中。就像 ICAM-1 一样。体外肾皮质小管和肾小球系膜细胞中的 VCAM-1 也会被 TNF-α 上调。 IL-1 和 IFN-γ。 T 细胞和小噬细胞系通过使用 VCAM-1/VLA-4 和 ICAM-1/LFA-1 结合对粘附到 TNF-α 刺激的肾小管上皮细胞上。与正常肾脏切片相比，来自肾病 MRL/lpr 的肾脏组织切片还显示出 T 细胞和巨噬细胞系以及 MRL/lpr 淋巴结细胞的粘附性增加。 MRL/lpr 肾组织的这种增强的粘附性可被针对 VCAM-1 和 ICAM-1 分子的单克隆抗体抑制。因此，VCAM-1和ICAM-1充当肾实质粘附分子并介导小鼠狼疮性肾炎中致病性炎症细胞的粘附。
Vascular cell adhesion molecule-1 (VCAM-1) is a cell surface protein which mediates adherence of inflammatory cells to target cells by binding with the beta-1-integrin ligand Very Late Antigen-4 (VLA-4) on leukocytes. The expression of VCAM-1 was investigated in a murine model of lupus nephritis, the autoimmune MRL/lpr mouse. Compared with normal mice, MRL/lpr kidneys show increased VCAM-1 expression not only in the endothelium, but also in cortical tubules and glomeruli. Increased steady-state VCAM-1 mRNA levels (approximately 3 kB) are detected in the kidney of nephritic MRL/lpr mice. Two additional transcripts (approximately 2 and approximately 1.8 kB) are present in autoimmune MRL/lpr but not in normal mice. Like ICAM-1. VCAM-1 is also upregulated in vitro in renal cortical tubular and mesangial cells by TNF-alpha. IL-1 and IFN-gamma. T cell and microphage cell lines adhere to TNF-alpha stimulated tubular epithelial cells by using the VCAM-1/VLA-4 and the ICAM-1/LFA-1 binding pairs. Kidney tissue sections from nephritic MRL/lpr also display increased adhesiveness for T cell and macrophage cell lines, and for MRL/lpr lymph node cells when compared with normal kidney sections. This enhanced adhesiveness of MRL/lpr kidney tissue is inhibited with monoclonal antibodies targeting the VCAM-1 and ICAM-1 molecule. Thus, VCAM-1 and ICAM-1 function as renal parenchymal adhesion molecules and mediate the adherence of pathogenic inflammatory cells in murine lupus nephritis.