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

Kidney Int. 1992 Oct;42(4):903-14. doi: 10.1038/ki.1992.367.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Adhesion Molecules / analysis*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology
  • Female
  • Intercellular Adhesion Molecule-1
  • Kidney Tubules / cytology
  • Lupus Nephritis / metabolism*
  • Lymphocyte Function-Associated Antigen-1 / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • RNA, Messenger / analysis
  • Receptors, Very Late Antigen / analysis
  • Receptors, Very Late Antigen / physiology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1

Substances

  • Cell Adhesion Molecules
  • Lymphocyte Function-Associated Antigen-1
  • RNA, Messenger
  • Receptors, Very Late Antigen
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1