Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in autoimmune murine lupus nephritis.
Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein regulating interactions among immune cells. To determine whether altered expression of ICAM-1 occurs in autoimmune lupus nephritis, we studied ICAM-1 expression in kidneys of normal and autoimmune MRL-lpr and (NZBX NZW)F1 (NZB/W) mice. By immunoperoxidase staining, ICAM-1 is constitutively expressed at low levels in proximal tubules (PT), endothelium and interstitial cells in normal C3H/FeJ mice. In nephritic MRL-lpr and NZB/W kidneys, staining for ICAM-1 is increased in the PT, particularly in the brush border, and is prominent in the glomerular mesangium and the endothelium of large vessels. By Western blot analysis, ICAM-1 is not detected in the urine of normal BALB/c and C3H/FeJ or autoimmune MRL-lpr. By Northern blot analysis, nephritic MRL-lpr and NZB/W have a two- to fivefold increase in steady state levels of ICAM-1 transcripts in the kidney as compared with normal or prenephritic mice. This is paralleled by an increase in MHC class II transcripts. In cultured PT cells, ICAM-1 is expressed at basal levels in PT and is increased by the cytokines interferon-gamma, IL-1 alpha, and TNF-alpha. Thus cytokine-mediated upregulation of ICAM-1 in lupus nephritis may promote interaction of immune cells with renal tissue. The predominant apical expression of ICAM-1 opposite to the basolateral Ia expression suggests a novel role for this adhesion molecule in PT.
Wuthrich
R P
RP
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Jevnikar
A M
AM
Takei
F
F
Glimcher
L H
LH
Kelley
V E
VE
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005920:Glomerular Mesangium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008871:Microvilli / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology
D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1