Mechanism of inflammatory cell infiltration in the kidney tissue of glomerulonephritis and diabetic nephropathy. -Elucidation of the role of cell adhesion molecules and development of therapeutic drugs.-

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In STZ-induced diabetic rat, we investigated the macrophage infiltration into the glomeruli and expression of ICAM-1. After induction of the diabetes, ICAM-1 was upregulated in the glomeruli. In addition, intraglomerular macrophage infiltration was observed. By the normalization of the blood glucose levels by insulin injection, expression of ICAM-1 and macrophage infiltration were prevened. These results indicated that ICAM-1 may paly a pivotal role in the macrophage infiltration of the diabetic nephropathy.We examined the expression of P-and E-selectins in the kidney tissues by immunohistochemistry. Normal kidney specimens and kidney biopsy specimens of glomerulonephritis and diabetic nephropathy patients were used. In normal kidneys, P-and E-selections were not detected. In lupus nephritis and diabetic nephropathy, P- and E-selections were expressed in the glomeruli and the intertubular vessels. Selections may be involved in the leukocyte infiltration into the kidney tissues in lupus nephritis and diabetic nephropathy.By using the L-selectin-IgG chimeric molecule (LEC-IgG), the distribution of L-selectin ligands were investigated. L-selectin ligands were distributed on the distal tubular epithelium. After ligation of ureters of rats, L-selectin ligands were disappeared from the tubular cells and redistributed intertubular vessels. Tubular monocyte infiltraion was also observed. By th e injection of sulfatide and and anti-L-selectin antibody, monocyte infiltration was inhibited. Monocyte adhesive pathway via L-selectin may play a key role in the monocute infiltration into the kidney tissue in rat ureter ligation animal model.