Elsevier

Kidney International

Volume 42, Issue 4, October 1992, Pages 903-914
Kidney International

Laboratory Investigation
Vascular cell adhesion molecule-1 (VCAM-1) expression in murine lupus nephritis

https://doi.org/10.1038/ki.1992.367Get rights and content
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Vascular cell adhesion molecule-1 (VCAM-1) expression in murine lupus nephritis. 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 β1-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 (∼3 kB) are detected in the kidney of nephritic MRL/lpr mice. Two additional transcripts (∼2 and ∼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-α, IL-1 and IFN-γ. T cell and macrophage cell lines adhere to TNF-α 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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