Abstract:
BACKGROUND:Wegener's granulomatosis (WG) is characterized by systemic vasculitis with crescentic glomerulonephritis (CGN) and circulating autoantibodies directed against neutrophil cytoplasmic antigens (ANCA). Proteinase 3 (PR-3), a neutral serine proteinase in neutrophils implicated in the growth control of myeloid cells, has been identified as the target antigen for ANCA in WG. Since the kidneys are frequently involved in WG, we studied the in situ expression of PR-3 by renal parenchymal cells. METHODS:We assessed the expression of PR-3 in kidney biopsies of 15 patients with WG by immunohistochemistry (IHC) and in situ hybridization (ISH). Normal kidney tissue served as the control. RESULTS:We detected PR-3 mRNA and PR-3 protein in distal tubular epithelial cells (TECs) and glomerular epithelial cells (GECs) in normal kidney tissue and in CGN. Furthermore, a strong glomerular PR-3mRNA expression restricted to the site of cellular crescents was detected in patients with WG. The analysis of 144 glomeruli with cellular or sclerotic crescents revealed a positive correlation of glomerular PR-3mRNA expression with the percentage of cellular crescents per glomerulus. The capability of human TECs and GECs to synthesize PR-3 was confirmed by Northern blot and ISH on cultured cells. CONCLUSION:These data provide evidence that nonhematopoetic renal parenchymal cells express PR-3 and that glomerular expression of PR-3 is associated with crescent formation in WG. Our findings suggest that renal parenchymal cells may directly be involved in the pathogenesis of CGN in WG.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Schwarting A,Hagen D,Odenthal M,Brockmann H,Dienes HP,Wandel E,Rumpelt HJ,Zum Büschenfelde KH,Galle PR,Mayet Wdoi
10.1046/j.1523-1755.2000.00100.xsubject
Has Abstractpub_date
2000-06-01 00:00:00pages
2412-22issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)47000-0journal_volume
57pub_type
杂志文章abstract::Emerging evidence of crosstalk between glomerular cells in pathological settings provides opportunities for novel therapeutic discovery. Here we investigated underlying mechanisms of early events leading to filtration barrier defects of podocyte and glomerular endothelial cell crosstalk in the mouse models of primary ...
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journal_title:Kidney international
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journal_title:Kidney international
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pub_type: 杂志文章
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更新日期:2003-11-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
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journal_title:Kidney international
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00631.x
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journal_title:Kidney international
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journal_title:Kidney international
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Kidney international
pub_type: 杂志文章
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journal_title:Kidney international
pub_type: 杂志文章
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更新日期:1996-04-01 00:00:00
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更新日期:2007-10-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
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更新日期:1994-05-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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