Cell adhesion molecule expression in murine lupus-like nephritis induced by lipopolysaccharide.
BACKGROUND
Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM) are thought to play important roles in leukocyte recruitment to the kidney. We therefore chose to study mesangial cell adhesion molecule expression in vitro, and the role of these molecules in experimental lupus-like nephritis.


RESULTS
When cultured murine mesangial cells were stimulated with interferon-gamma (IFgamma) and tumor necrosis factor-alpha (TNFalpha), mRNA levels for ICAM-1 and VCAM markedly increased. These molecules were detected at the cell surface by flow cytometry. Since lipopolysaccharide (LPS) stimulates TNFalpha and IFgamma production in vivo, we treated mice with Streptococcus minnesota LPS in order to study renal adhesion molecule expression. LPS treatment induced mesangial proliferative glomerulonephritis characterized by leukocyte infiltration, and increases in total glomerular cellularity, volume and matrix area. mRNA levels for ICAM-1 and VCAM were increased in the kidneys of LPS-treated versus control mice. ICAM-1 and VCAM molecules were constitutively expressed in renal vascular endothelium. At 3 and 5 weeks, this vascular staining intensified, and some ICAM-1 and VCAM expression was induced in the glomerular mesangium. ICAM-1 and VCAM induction occurred early and correlated in time with leukocyte infiltration.


CONCLUSIONS
Interactions between cell adhesion molecules expressed by intrinsic glomerular cells and infiltrating leukocytes play a role in the initiation of LPS-induced lupus-like nephritis. These observations are potentially relevant to the understanding and treatment of certain types of human glomerulonephritis.
Baran
D
D
McGill University, Montreal, Quebec, Canada. mcdn@musica.mcgill.ca
Vendeville
B
B
Ogborn
M
M
Katz
N
N
D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008181:Lupus Nephritis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D013291:Streptococcus; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics*
D017931:DNA Primers; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma