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Titolo:
Complement-mediated killing of mesangial cells in experimental glomerulonephritis: Cell death by a combination of apoptosis and necrosis
Autore:
Shimizu, A; Masuda, Y; Kitamura, H; Ohashi, R; Sugisaki, Y; Yamanaka, N;
Indirizzi:
Nippon Med Sch, Dept Pathol, Bunkyo Ku, Tokyo 1138602, Japan Nippon Med Sch Tokyo Japan 1138602 thol, Bunkyo Ku, Tokyo 1138602, Japan
Titolo Testata:
NEPHRON
fascicolo: 2, volume: 86, anno: 2000,
pagine: 152 - 160
SICI:
0028-2766(200010)86:2<152:CKOMCI>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXPERIMENTAL MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS; MOLECULAR-BIOLOGY; RAT; PERFORIN; ONCOSIS; IDENTIFICATION; CYTOTOXICITY; ANTIBODIES; MECHANISMS; PATHWAYS;
Keywords:
apoptosis; complement; glomerulonephritis; membrane attack complex; mesangial cell; necrosis; oncosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Shimizu, A Nippon Med Sch, Dept Pathol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138602, Japan Nippon Med Sch 1-1-5 Sendagi Tokyo Japan 1138602 138602, Japan
Citazione:
A. Shimizu et al., "Complement-mediated killing of mesangial cells in experimental glomerulonephritis: Cell death by a combination of apoptosis and necrosis", NEPHRON, 86(2), 2000, pp. 152-160

Abstract

Immune system mediated, particularly antibody- and complement-mediated, glomerular injury triggers glomerulonephritis (GN). To characterize complement-mediated cytotoxicity in GN, we assessed the process of mesangial cell death induced by C5b-9 attack in Thy-1 GN. Cell injury was recognized morphologically, and nuclear DNA breaks were confirmed by the DNA nick end labeling (TU NEL) method as well as DNA gel electrophoresis. Thy-1 GN was induced in rats with anti-Thy-1.1 antibody injection. Mouse IgG (administered antibody) and rat C3 were detected in all glomeruli within 5 min after antibody injection. Damaged mesangial cells with condensed as well as TUNEL-positivenuclei could be observed at 20 min and became prominent at 40-60 min. Ultrastructurally, damaged mesangial cells contained condensed apoptotic nucleifrom 40 to 60 min, whereas the cytoplasm showed necrotic degeneration. This was followed by progressive lysis of both nuclei and cyto-plasm. The DNA 'ladder' pattern was observed by gel electrophoresis of extracted DNA between 40 and 60 min and correlated with the increased number of TUNEL-positivedamaged mesangial cells. To examine the role of complement in this form ofcell death, complement depletion was induced in rats by cobra venom factor. Complement-depleted rats showed no rat C3 deposition, rare TUNEL-positivemesangial cells, rare ultrastructural degenerated mesangial cells with apoptotic nuclei and necrotic cytoplasm, and no DNA 'ladder' pattern on gel electrophoresis at 40 min, although prominent mouse IgG was seen in glomeruli. To analyze milder forms of complement injury, a low dose of the antibody was administered to rats with a normal complement level. A few TUNEL-positive mesangial cells were detected in the glomeruli which contained apoptoticnuclei and necrotic cytoplasm. Our results indicate that an apoptotic death mechanism accompanies cell necrosis in complement-mediated mesangial celldestruction in GN and that this unusual form of cell death may represent acombination of apoptosis-necrosis within the same cell. Complement injury activates a 'death program' which in turn leads to irreversible damage of mesangial cells and which may contribute to initiation and development of GN. Copyright (C) 2000 S.Karger AG, Basel.

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Documento generato il 29/09/20 alle ore 10:29:29