Application of anti-cell adhesion molecule therapies for renal diseases.

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We have investigated the possibility of application of anti-cell adhesion molecule therapies for renal diseases. In summary,1. We showed the up-regulated expression of ICAM-1, E-selectin and P-selectin in the glomeruli and interstitium of the kidney or the patients with glomerulonephritis and diabetic nephropathy.2. We calrified the mechanism that glomerular hyperfiltration induces intraglomerular expression of ICAM-1 and infiltration of macrophages.3. We showed that the ligands for L-selectin exist in the cytoplasm of tubular epithelial cells and re-distribute to the interstitium and peritubular capillaries after ureteral ligation in rat kidney. Furthermore, we showed that one of the ligands for L-selectin is sulfatide.4. We showed that administration of sulfatide which is a ligand for L- and P-selectin inhibits the infiltration of macrophage to renal interstitium in vivo.5. We showed that prostaglandin I_2 ameliorates renal injury by inhibition of ICAM-1 expression in rat crescentic glomerulonephritis model.These results showed the critical role of ICAM-1 and selectins for the infiltration of macrophege into renal tissues in various types of glomerular diseases. In conclusion, our results suggest the beneficial effects of anti-cell adhesion molecule therapy for glomerular diseases.