Renal expression of matrix metalloproteinases in human ANCA-associated glomerulonephritis
article
Background. Expression of matrix metalloproteinases (MMPs) by infiltrating and intrinsic renal cells is increased in inflammatory conditions, and may correlate with disease activity of glomerulonephritis. We analysed renal expression of MMPs, tissue inhibitor of metalloproteinase-1 (TIMP-1) and markers of neutrophil and monocyte infiltration in renal biopsies of patients with active anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Methods. Immunohistochemical expression of MMP-2, -3, -9, TIMP-1, the neutrophil- and monocyte-derived MMP activators cathepsin G, neutrophil elastase and myeloperoxidase (MPO), and the monocyte marker CD 14 was determined in renal biopsies of active proteinase 3 (PR3)-ANCA (n = 7) and MPO-ANCA (n = 6) associated glomerulonephritis, and in normal renal tissue (n = 4). Double labelling experiments of MMPs and TIMP-1 were performed with MPO and CD68, labelling neutrophils and macrophages. Results. MMP-2-, MMP-3-, MMP-9- and TIMP-1-positive cells were detected in ANCA-associated glomerulonephritis in glomeruli with active inflammation (cellular crescents or fibrinoid necrosis), only occasionally in normal appearing glomeruli, and not in sclerotic glomeruli and positive cells were found in the tubulo-interstitium. MMPs and TIMP-1 were expressed predominantly by MPO-and CD68-positive cells. In normal renal tissue, no expression was detected, with the exception of weak mesangial staining for MMP-2. In ANCA-associated glomerulonephritis, glomerular MMP-2, -9 and TIMP-1 correlated with glomerular cathepsin G expression, while the number of MMP-9-expressing cells per glomerulus correlated with the percentage of crescentic glomeruli. Tubulo-interstitial expression of MMPs correlated with all markers of neutrophil and monocyte infiltration, and interstitial MMP-9 and TIMP-1 expression correlated with renal function at the time of renal biopsy. Conclusions. Expression of glomerular and interstitial MMP-2, -3, -9 and TIMP-1 is increased in active ANCA-associated glomerulonephritis and correlates with inflammatory activity. © ERA-EDTA 2004; all rights reserved. Chemicals / CAS: cathepsin G, 56645-49-9; gelatinase A, 146480-35-5; gelatinase B, 146480-36-6; leukocyte elastase, 109968-22-1; myeloblastin, 128028-50-2; stromelysin, 79955-99-0; tissue inhibitor of metalloproteinase 1, 140208-24-8; Antibodies, Antineutrophil Cytoplasmic; Matrix Metalloproteinase 2, EC 3.4.24.24; Matrix Metalloproteinase 3, EC 3.4.24.17; Matrix Metalloproteinase 9, EC 3.4.24.35; Matrix Metalloproteinases, EC 3.4.24.-; Tissue Inhibitor of Metalloproteinase-1
Topics
Biomedical ResearchANCA-associated glomerulonephritisEnzyme inhibitorsExtracellular matrixImmunohisto-chemistryMatrix metalloproteinasescathepsin GCD14 antigenCD68 antigencell markergelatinase Agelatinase Bleukocyte elastasematrix metalloproteinasemyeloblastinmyeloperoxidaseneutrophil cytoplasmic antibodystromelysintissue inhibitor of metalloproteinase 1cell infiltrationcell labelingclinical articlecontrolled studycorrelation analysisglomerulonephritisglomerulosclerosisglomerulushuman tissueimmunohistochemistrykidney biopsykidney fibrosiskidney interstitiumkidney necrosiskidney tubulemonocyteneutrophilprotein expressionrapidly progressive glomerulonephritisAdultAgedAged, 80 and overAntibodies, Antineutrophil CytoplasmicGlomerulonephritisHumansImmunohistochemistryKidneyMatrix Metalloproteinase 2Matrix Metalloproteinase 3Matrix Metalloproteinase 9Matrix MetalloproteinasesMiddle AgedTissue Inhibitor of Metalloproteinase-1
TNO Identifier
237783
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ISSN
09310509
Source
Nephrology Dialysis Transplantation, 19(6), pp. 1412-1419.
Pages
1412-1419
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