Decreased PMN accumulation and glomerular damage by clodronate liposome treatment in PMN-dependent anti-GBM nephritis in mice.
GW Feith, MJ Bogman, KJ Assmann… - Experimental …, 1997 - europepmc.org
GW Feith, MJ Bogman, KJ Assmann, AP Van Gompel, J Schalkwijk, N Van Rooijen…
Experimental Nephrology, 1997•europepmc.orgBackground Intravenous administration of clodronate (dichloromethylene bisphosphate)-
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 used clodro-L treatment to study the role of M phi in a PMN-dependent model
of anti-glomerular basement membrane (GBM) nephritis. Methods C57BL/6J mice received
clodro-L iv at days-2 and-1 before iv injection of anti-GBM antibodies. The albuminuria of the …
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 used clodro-L treatment to study the role of M phi in a PMN-dependent model
of anti-glomerular basement membrane (GBM) nephritis. Methods C57BL/6J mice received
clodro-L iv at days-2 and-1 before iv injection of anti-GBM antibodies. The albuminuria of the …
Background
Intravenous administration of clodronate (dichloromethylene bisphosphate)-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 used clodro-L treatment to study the role of M phi in a PMN-dependent model of anti-glomerular basement membrane (GBM) nephritis.
Methods
C57BL/6J mice received clodro-L iv at days-2 and-1 before iv injection of anti-GBM antibodies. The albuminuria of the first 24 h was measured by radial immunodiffusion in 18 hour urine samples and glomerular changes were studied histologically and immunohistologically.
Results
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, clodro-L-pretreated C57BL/6J mice showed considerable reduction of both albuminuria and glomerular damage at day 1 after injection of rabbit anti-GBM antibody.
Conclusions
In this PMN-dependent model, the inhibitory effect of clodro-L treatment on the development of nephritis very likely due to the inhibition of glomerular PMN accumulation. Our results indicate the clodro-L treatment as a method of selective M phi depletion has its limitations, especially in models in which PMN are involved as effector cells.
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