bromochloroacetic-acid and Anti-Glomerular-Basement-Membrane-Disease

To examine the cellular components at different stages of the crescent formation in four most common types of human crescentic glomerulonephritis (CGN), including anti-GBM disease (GBM-CGN), crescentic IgA nephropathy (IgA-CGN), ANCA associated pauci-immune CGN (ANCA-CGN) and crescentic lupus glomerulonephritis (LN-CGN).. Renal biopsy specimens of patients with GBM-CGN (n = 10), IgA-CGN (n = 12), ANCA-CGN (n = 12), and LN-CGN (n = 11) were selected. Immunohistochemistry was adopted to identify the cellular components using different cell markers including cytokeratin (PEC), CD68 (macrophage), nestin (podocyte), podocalyxin (podocyte), CD3 (lymphocyte), CD15 (neutrophil) and PCNA.. There were different subtypes of cell components identified during the formation of a cellular crescent in 4 different types of human CGN. Mainly of PEC 11.4 (0.0, 95.0)%, macrophage 8.0 (0.0, 35.0)% and podocyte 5.5 (0.0, 22.0)% and their constitutive percentages were different among various CGNs (P < 0.01). In all the CGNs studied, there were 50% of cells were negative to all the cell markers adopted for this expeiment. Podocalyxin positive cells 0.5 (0.0, 9.6)% were significantly less than nestin positive cells 5.5 (0.0, 22.0)% in all CGNs. PCNA positive cells were 44.7 (16.7, 83.3)% in the cellular crescent of all CGNs and co-localized with nestin (38/45 cases), CK (42/45 cases) or CD68 (24/45 cases).. PEC, macrophage and podocyte might play important roles in the formation of crescents. The staining disparity of nestin and podocalyxin indicates that podocyte dedifferentiation may occur during the crescent formation. PEC, podocytes and macrophages may participate in the formation of crescent in common CGNs through active cellular proliferation.

Topics: Anti-Glomerular Basement Membrane Disease; Antibodies, Antineutrophil Cytoplasmic; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cell Proliferation; Epithelial Cells; Glomerulonephritis; Glomerulonephritis, IGA; Humans; Intermediate Filament Proteins; Keratins; Lupus Nephritis; Macrophages; Nerve Tissue Proteins; Nestin; Podocytes; Proliferating Cell Nuclear Antigen; Sialoglycoproteins

The role of podocytes in human crescentic glomerulonephritis (GN) has been underestimated. This may be due to the confounding fact that "dysregulated" podocytes are able to proliferate, lose their markers, and acquire new epitopes. Moreover, in experimental anti-glomerular basement membrane (GBM) crescentic GN, podocytes participate in the crescent formation. The aim of this study was to investigate the involvement of podocytes in human immune crescentic GN.. Renal biopsies from 12 patients with anti-GBM disease and 14 with class IV lupus GN were studied by immunohistochemistry for the following markers: (1) synaptopodin, GLEPP1, podocalyxin, podocin, alpha-actinin-4, and vimentin for podocyte identification; (2) PCNA, Ki-67, and p57 for cell cycle assessment; (3) cytokeratins for identifying epithelial cells but not normal podocytes; (4) CD68 for tagging a macrophagic epitope; (5) alpha-smooth-muscle actin (alpha-SMA), a phenotypic marker of myofibroblasts.. "True" (capsular) crescents lining Bowman's capsule and (tuft) "pseudocrescents" covering the glomerular tuft with a persistent patent urinary space were present in the 2 types of crescentic GN in similar percentages. Several features indicated that podocytes were involved in the formation of the both crescent types. Identifiable podocytes expressed proliferation markers. Podocyte cytoplasmic expansions and racket-like podocytes bridged between the tuft and Bowman's capsule. True and pseudocrescents contained labeled podocytes. In addition, podocytes located outside of the crescents had often lost their markers (dedifferentiation) and acquired new epitopes (cytokeratins and CD68).. In human immune crescentic GN, podocytes undergo proliferation and dysregulation that are indicative of a podocytopathy. Podocytes contribute to crescent formation.

Topics: Actins; Adult; Aged; Anti-Glomerular Basement Membrane Disease; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Biopsy; Cyclin-Dependent Kinase Inhibitor p57; Female; Humans; Keratins; Ki-67 Antigen; Lupus Nephritis; Macrophages; Male; Middle Aged; Podocytes; Proliferating Cell Nuclear Antigen; Vimentin