Decreased PMN accumulation and glomerular damage by clodronate liposome treatment in PMN-dependent anti-GBM nephritis in mice.
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 i.v. at days -2 and -1 before i.v. 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.
Feith
G W
GW
Department of Pathology, University Hospital Nijmegen, The Netherlands.
Bogman
M J
MJ
Assmann
K J
KJ
van Gompel
A P
AP
Schalkwijk
J
J
van Rooijen
N
N
Koene
R A
RA
D000419:Albuminuria; D000818:Animals; D000906:Antibodies; D002462:Cell Membrane / Q000276:immunology; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004337:Drug Carriers; D005921:Glomerulonephritis / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits
D000906:Antibodies; D004337:Drug Carriers; D008081:Liposomes; D004002:Clodronic Acid