VCAM-1
狼疮性肾炎
细胞粘附分子
肾
淋巴细胞功能相关抗原1
细胞粘附
肾小球肾炎
免疫学
分子生物学
医学
生物
细胞间粘附分子-1
ICAM-1
病理
内分泌学
细胞
生物化学
疾病
作者
Rudolf P. Wüthrich,Tracey Snyder
摘要
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 macrophage 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 molecules. Thus, VCAM-1 and ICAM-1 function as renal parenchymal adhesion molecules and mediate the adherence of pathogenic inflammatory cells in murine lupus nephritis.
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