Long-term observation of glomerulonephritis induced by multiple injections with anti-Thy-1 antibody in rats.
Multiple injections with a mouse monoclonal anti-rat Thy-1 antibody (five times, at weekly intervals) induced marked glomerular sclerotic lesions which are characterized by adhesion of glomerular capillaries to Bowman's capsule and persistent proteinuria in rats. Abnormal production of type I collagen and increased accumulation of type IV collagen and fibronectin were observed in these glomeruli. The glomerular expression of mRNA for these matrix components and transforming growth factor-beta1 (TGF-beta1) were markedly increased at 4 days after the last injections with anti-Thy-1 antibody, but decreased to below the levels of control rats at 5 weeks. This may be down-regulation of mRNA in mesangial cells. The glomerular sclerotic lesions were not progressive but the process of glomerular healing seemed to be retarded. The proteinuria and the glomerular adhesion were irreversible.
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd, Takasaki, Gunma, Japan. m-yagi@kirin.co.jp
M
M
Yagi
T
T
Yamamoto
S
S
Kato
N
N
Nagano
I
I
Kihara
D000818:Animals; D000911:Antibodies, Monoclonal; D001806:Blood Urea Nitrogen; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007267:Injections; D007518:Isoantibodies; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D007518:Isoantibodies; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C035678:anti-Thy antibody; D003094:Collagen