TY - JOUR
T1 - Distribution of the granulocyte serine proteinases proteinase 3 and elastase in human glomerulonephritis
AU - Mrowka, Christian
AU - Csernok, ELENA
AU - Gross, Wolfgang L.
AU - Feucht, Helmut E.
AU - Bechtel, Ulrike
AU - Thoenes, Gunther H.
N1 - Funding Information:
For immunohistologic studies, unfixed renal tissue was embedded and shock-frozen in a mixture of fluid nitrogen and methylbutan. Cryostat sections 4 pm thick were prepared and air dried. Immunofluorescence analysis was performed in unfixed sections using fluorescein-isothiocyanate-labeled rabbit antibodies against human fibrinogen, immunoglobulin From the Medical Clinic II, University of Aachen, Aachen; the Department of Clinical Rheumatology, Medical University of Liibeck and Rheumaklinik Bad Bramstedt, Bad Bram-stedt; and the Medical Clinic Innenstadt, University of Munich, Munich, Germany. Received November 8, 1993; accepted in revisedform tember 12, 1994. Presented in part at The Fifth International shop, Cambridge, United Kingdom, 1993. Dr Mrowka is supported by the Deutsche Forschungsge-meinschafr DFG, grant no. AZ Mr IS/l-l. Address reprint requests to Christian Mrowka, MD, Medical Clinic II, RWTH Aachen, Pauwelsstr. 30, 52057 Aachen, Germany. 0 1995 by the National Kidney Foundation, 0272-6386/95/2502-0006$3.00/O
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 1995/2
Y1 - 1995/2
N2 - The serine proteinases proteinase 3 (PR3) and elastase are target antigens of antineutrophil cytoplasmic autoantibodies (ANCAs), which are found in various systemic vasculitides with rapidly progressive glomerulonephritis (RPGN). The expression of both proteinases was studied immunohistologically (avidin-biotin complex method) with murine monoclonal antibodies against PR3 (WGM2) and elastase (NP 57) in 122 human renal biopsy specimens to investigate their role in mediating renal damage. Expression of PR3 predominated in ANCA-associated RPGN and was independent of the serologic ANCA pattern (c-/p-ANCA). The PR3 staining pattern was patchy and not always related to distinct granulocytes due to antigen spreading by disintegrating cells. It was found in crescentic glomeruli and the interstitium of ANCA-positive RPGN. In contrast, glomerular and interstitial elastase staining pattern was much more granulocyte related and was even found in noncrescentic glomeruli in c-ANCA- and p-ANCA-positive pauci-immune RPGN. Endothelial cell and glomerular basement membrane-bound PR3 or elastase expression were not observed. A faint glomerular PR3/elastase expression was seen in Goodpasture's syndrome and within the interstitium in crescentic mesangioproliferative glomerulonephritis (granulocyte related). Both serine proteinases were found in the glomeruli in ANCA-negative acute postinfectious glomerulonephritis. In conclusion, this study provides evidence, for the first time, for the implication of the granulocyte serine proteinases PR3 and elastase in mediating pauci-immune ANCA-positive RPGN and different forms of proliferative glomerulonephritis. The expression of ANCA antigens in ANCA-negative glomerulonephritis suggests that this finding is a marker of neutrophil activation. The role of circulating antibodies (ANCA) in mediating the development of the characteristic pauci-immune RPGN and systemic vasculitis remains to be elucidated.
AB - The serine proteinases proteinase 3 (PR3) and elastase are target antigens of antineutrophil cytoplasmic autoantibodies (ANCAs), which are found in various systemic vasculitides with rapidly progressive glomerulonephritis (RPGN). The expression of both proteinases was studied immunohistologically (avidin-biotin complex method) with murine monoclonal antibodies against PR3 (WGM2) and elastase (NP 57) in 122 human renal biopsy specimens to investigate their role in mediating renal damage. Expression of PR3 predominated in ANCA-associated RPGN and was independent of the serologic ANCA pattern (c-/p-ANCA). The PR3 staining pattern was patchy and not always related to distinct granulocytes due to antigen spreading by disintegrating cells. It was found in crescentic glomeruli and the interstitium of ANCA-positive RPGN. In contrast, glomerular and interstitial elastase staining pattern was much more granulocyte related and was even found in noncrescentic glomeruli in c-ANCA- and p-ANCA-positive pauci-immune RPGN. Endothelial cell and glomerular basement membrane-bound PR3 or elastase expression were not observed. A faint glomerular PR3/elastase expression was seen in Goodpasture's syndrome and within the interstitium in crescentic mesangioproliferative glomerulonephritis (granulocyte related). Both serine proteinases were found in the glomeruli in ANCA-negative acute postinfectious glomerulonephritis. In conclusion, this study provides evidence, for the first time, for the implication of the granulocyte serine proteinases PR3 and elastase in mediating pauci-immune ANCA-positive RPGN and different forms of proliferative glomerulonephritis. The expression of ANCA antigens in ANCA-negative glomerulonephritis suggests that this finding is a marker of neutrophil activation. The role of circulating antibodies (ANCA) in mediating the development of the characteristic pauci-immune RPGN and systemic vasculitis remains to be elucidated.
UR - http://www.scopus.com/inward/record.url?scp=0028795536&partnerID=8YFLogxK
U2 - 10.1016/0272-6386(95)90006-3
DO - 10.1016/0272-6386(95)90006-3
M3 - Journal articles
C2 - 7847352
AN - SCOPUS:0028795536
SN - 0272-6386
VL - 25
SP - 253
EP - 261
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -