Proteinase-3 mRNA expressed by glomerular epithelial cells correlates with crescent formation in Wegener's granulomatosis.

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 Int

journal_title

Kidney international

authors

Schwarting A,Hagen D,Odenthal M,Brockmann H,Dienes HP,Wandel E,Rumpelt HJ,Zum Büschenfelde KH,Galle PR,Mayet W

doi

10.1046/j.1523-1755.2000.00100.x

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

2412-22

issue

6

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)47000-0

journal_volume

57

pub_type

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