Cell adhesion molecule expression in murine lupus-like nephritis induced by lipopolysaccharide

Background Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adh esion molecule (VCAM) are thought to play important roles in leukocyte recr uitment to the kidney. We therefore chose to study mesangial cell adhesion molecule expression in vitro, and the role of these molecules in experiment al lupus-like nephritis. Methods and Results: When cultured murine mesangia l cells were stimulated with interferon-gamma (IF gamma) and tumor necrosis factor-alpha (TNF alpha), mRNA levels for ICAM-1 and VCAM markedly increas ed. These molecules were detected at the cell surface by flow cytometry. Si nce lipopolysaccharide (LPS) stimulates TNF alpha and IF gamma production i n vivo, we treated mice with Streptococcus minnesota LPS in order to study renal adhesion molecule expression. LPS treatment induced mesangial prolife rative glomerulonephritis characterized by leukocyte infiltration, and incr eases in total glomerular cellularity, volume and matrix area. mRNA levels for ICAM-1 and VCAM were increased in the kidneys of LPS-treated versus con trol 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 mesangi um. ICAM-1 and VCAM induction occurred early and correlated in time with le ukocyte infiltration. Conclusion: Interactions between cell adhesion molecu les expressed by intrinsic glomerular cells and infiltrating leukocytes pla y a role in the initiation of LPS-induced lupus-like nephritis. These obser vations are potentially relevant to the understanding and treatment of cert ain types of human glomerulonephritis. Copyright (C) 2000 S. Karger AG, Bas el.