DECREASED PMN ACCUMULATION AND GLOMERULAR DAMAGE BY CLODRONATE LIPOSOME TREATMENT IN PMN-DEPENDENT ANTI-GEM NEPHRITIS IN MICE

Background: Intravenous administration of clodronate (dichloromethylen e bisphosphonate)-containing liposomes (clodro-L) has been reported to induce selective depletion of tissue macrophages (M Phi) with little or no effect on polymorphonuclear granulocytes (PMN). Therefore, we us ed clodro-L treatment to study the role of M Phi in a PMN-dependent mo del of anti-glomerular basement membrane (GEM) nephritis. Methods: C57 BL/6J mice received clodro-L i.v. at days -2 and -1 before the i.v. in jection of anti-GBM antibodies. The albuminuria of the first 24 h was measured by radial immunodiffusion in 18 hour urine samples and glomer ular changes were studied histologically and immunohistologically. Res ults: Treatment with clodro-L, in doses that adequately destroyed the Kupffer cells, failed to reduce glomerular M Phi numbers, but markedly inhibited glomerular PMN accumulation. Compared to control mice, clod ro-L-pretreated C57BL/6J mice showed considerable reduction of both al buminuria and glomerular damage at day 1 after injection of rabbit ant i-GBM antibody. Conclusions: In this PMN-dependent model, the inhibito ry effect of clodro-L treatment on the development of nephritis is ver y likely due to the inhibition of glomerular PMN accumulation. Our res ults indicate that clodro-L treatment as a method of selective M Phi d epletion has its limitations, especially in models in which PMN are in volved as effector cells.