Anti-mouse mesangial cell serum induces acute glomerulonephropathy in mice.
In order to develop a model in mouse similar to anti- Thy-1 nephritis in the rat, we prepared sheep antiserum against SV40-transformed mouse mesangial (MES 13) cells. In vivo, the anti-mouse mesangial cell serum-treated mice showed severe azotemia that peaked at day 6 and proteinuria that peaked at day 8, in a dose-dependent fashion. Light microscopy and electron microscopy showed duplication of glomerular basement membranes, mesangiolysis, subendothelial and mesangial electron-dense deposits, and foot process effacement. Intraglomerular tuft cell number was significantly reduced at day 4 and there were increased numbers of apoptotic cells at days 2 and 4. SCID mice and mice lacking C3 manifested similar responses to anti-mouse mesangial cell serum, suggesting that T cells, B cells and complement are not required for glomerular injury in this model. In vitro, anti-mouse mesangial cell serum treated mesangial cells showed greater release of lactate dehydrogenase, decreased cell survival, and increased apoptotic cell death. Anti-mouse mesangial cell serum induces glomerulopathy characterized by mesangiolysis and mesangial cell apoptosis, and followed by cellular proliferation.
Yo
Yoshikage
Y
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892-1268, USA.
Braun
Michael C
MC
Barisoni
Laura
L
Mobaraki
Hideko
H
Lu
Huiyan
H
Shrivastav
Shashi
S
Owens
Jennie
J
Kopp
Jeffrey B
JB
D016475:3T3 Cells; D000208:Acute Disease; D000818:Animals; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004731:Endotoxins / Q000009:adverse effects / Q000097:blood; D005260:Female; D005920:Glomerular Mesangium / Q000737:chemistry / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000209:etiology* / Q000276:immunology; D007106:Immune Sera / Q000378:metabolism / Q000633:toxicity*; D007136:Immunoglobulins / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000276:immunology; D008168:Lung / Q000737:chemistry / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D009928:Organ Specificity; D012756:Sheep / Q000276:immunology; D013997:Time Factors
D000954:Antigens, Surface; D004731:Endotoxins; D007106:Immune Sera; D007136:Immunoglobulins