Cell Adhesion Molecule Expression in Murine Lupus-Like Nephritis Induced by Lipopolysaccharide

Abstract

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. Methods and Results: When cultured murine mesangial cells were stimulated with interferon-γ (IFγ) and tumor necrosis factor-α (TNFα), mRNA levels for ICAM-1 and VCAM markedly increased. These molecules were detected at the cell surface by flow cytometry. Since lipopolysaccharide (LPS) stimulates TNFα and IFγ 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. Conclusion: 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.