Suppression of anti-glomerular basement membrane nephritis by administration of anti-monocyte chemoattractant protein-1 antibody in WKY rats.
Anti-glomerular basement membrane (GBM) nephritis in WKY rats is characterized by an accumulation of CD8-positive lymphocytes (CD8+ lym) and monocytes/macrophages (Mo/M psi) in the glomeruli and crescent formation. In the study presented here, the involvement of a chemokine for Mo/M psi, monocyte chemoattractant protein-1 (MCP-1), was examined in this model. An intense induction of mRNA for MCP-1 in the glomeruli and a suppressive effect of anti-MCP-1 antibody administration on the glomerular Mo/M psi accumulation and proteinuria were found. MCP-1 mRNA was expressed intensely in the glomeruli 4 d after the anti-GBM antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of Mo/M psi infiltrating in the glomeruli decreased by 34.7% (19.6 +/- 7.1 versus 30.0 +/- 6.0 per glomerular cross-section, P < 0.01) and proteinuria by 66.2% (15.6 +/- 9.3 versus 46.1 +/- 15.1 mg/d, P < 0.01) at day 4. In contrast, the number of CD8+ lym accumulating in the glomeruli was not affected significantly (6.6 +/- 2.7 versus 6.0 +/- 3.0 per glomerular cross-section, P > 0.05). However, the treatment with the anti-MCP-1 antibody did not reduce Mo/M psi infiltration, urinary protein excretion, and crescent formation at day 8. These data suggest that MCP-1 plays a role in the glomerular accumulation of Mo/M psi, and that the infiltrating Mo/M psi cause glomerular injury and increased excretion of protein in the urine.
Fujinaka
H
H
Department of Pathology, Niigata University School of Medicine, Japan.
Yamamoto
T
T
Takeya
M
M
Feng
L
L
Kawasaki
K
K
Yaoita
E
E
Kondo
D
D
Wilson
C B
CB
Uchiyama
M
M
Kihara
I
I
D000818:Animals; D000911:Antibodies, Monoclonal; D001485:Basement Membrane / Q000276:immunology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009500:Neutralization Tests; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2; D012333:RNA, Messenger