Effect of mizoribine on glomerulonephritis of early-stage IgA nephropathy in ddY mice.
Immunopathological studies were performed to determine whether the glomerular injuries in ddY mice, a model for IgA nephropathy (Berger's disease), are influenced by treatment with mizoribine, a new immunosuppressive agent. The ddY mice were treated with a low (0.05 mg/ml) or a high (0.1 mg/ml) dose of mizoribine for 35 weeks. Flow cytometry analysis showed that there was a marked decrease in the number of B cells and IgA-bearing B cells. In immunofluorescence, the deposition of IgA in the glomerular mesangial areas and capillary walls of the high-dose mizoribine-treated ddY mice was markedly decreased as compared with that of control ddY mice receiving drinking water. The glomerular mesangial expansion in the high-dose mizoribine-treated ddY mice was milder than that found in the control ddY mice. In 45-week-old ddY mice, the average number of intraglomerular cells in the high-dose and low-dose mizoribine-treated ddY mice was slightly lower than that in drinking water treated ddY mice. The levels of urinary protein excretion in the high-dose mizoribine-treated ddY mice were also lower than those in the low-dose mizoribine-treated or drinking water treated ddY mice. It appears that treatment of mizoribine might influence the proliferation of B cells, especially IgA-bearing B cells, and improve the glomerular IgA deposition and glomerular expansion in early-stage IgA nephropathy of ddY mice.
Shimizu
M
M
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Shou
I
I
Tsuge
T
T
Abe
M
M
Tomino
Y
Y
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005920:Glomerular Mesangium / Q000473:pathology; D005921:Glomerulonephritis / Q000188:drug therapy*; D005922:Glomerulonephritis, IGA / Q000188:drug therapy*; D007070:Immunoglobulin A / Q000276:immunology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011507:Proteinuria; D012263:Ribonucleosides / Q000627:therapeutic use*
D007070:Immunoglobulin A; D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine