BACKGROUND: An increased number of major histocompatibility complex (MHC) class II-positive cells (OX-6+ cells) were observed in the glomerulus and periglomerular interstitium during the course of anti-glomerular basement membrane (anti-GBM) crescentic glomerulonephritis (GN) in WKY rats. This study aimed to demonstrate that periglomerular OX-6+ cells are dendritic cells (DCs) and to clarify their roles in the pathogenesis of this GN. METHODS: Kidney sections were stained with the OX-6 and the rat DC marker OX-62 by immunohistochemistry, and periglomerular OX-6+ cells were observed by immunoelectron microscopy. Renal mRNA expression for CXCL12 was examined by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization, and that for IL-1beta was examined by in situ hybridization. RESULTS: Immunohistochemistry revealed that most periglomerular OX-6+ cells in this GN were ED-1-negative. OX-62+ cells were observed sparsely in normal kidney interstitium, and considerably more frequently in periglomerular interstitium in this GN. Immunoelectron microscopy confirmed the periglomerular OX-6+ED-1- cells had DC morphology. The increased expression of CXCL12 mRNA in the diseased glomerulus was shown by RT-PCR. By in situ hybridization, CXCL12 mRNA-expressing glomerular cells were the parietal and visceral epithelial cells, which were close to the site of periglomerular OX-6+ cell localization. The intense expression of IL-1beta mRNA by periglomerular cells was demonstrated by in situ hybridization. CONCLUSIONS: The periglomerular distribution of OX-6+ED-1- DCs was demonstrated in anti-GBM crescentic GN in WKY rats. These DCs might be accumulated in periglomerular interstitium by CXCL12, and play a role in the initiation and progression of this GN by producing IL-1beta.
BACKGROUND: An increased number of major histocompatibility complex (MHC) class II-positive cells (OX-6+ cells) were observed in the glomerulus and periglomerular interstitium during the course of anti-glomerular basement membrane (anti-GBM) crescentic glomerulonephritis (GN) in WKY rats. This study aimed to demonstrate that periglomerular OX-6+ cells are dendritic cells (DCs) and to clarify their roles in the pathogenesis of this GN. METHODS: Kidney sections were stained with the OX-6 and the rat DC marker OX-62 by immunohistochemistry, and periglomerular OX-6+ cells were observed by immunoelectron microscopy. Renal mRNA expression for CXCL12 was examined by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization, and that for IL-1beta was examined by in situ hybridization. RESULTS: Immunohistochemistry revealed that most periglomerular OX-6+ cells in this GN were ED-1-negative. OX-62+ cells were observed sparsely in normal kidney interstitium, and considerably more frequently in periglomerular interstitium in this GN. Immunoelectron microscopy confirmed the periglomerular OX-6+ED-1- cells had DC morphology. The increased expression of CXCL12 mRNA in the diseased glomerulus was shown by RT-PCR. By in situ hybridization, CXCL12 mRNA-expressing glomerular cells were the parietal and visceral epithelial cells, which were close to the site of periglomerular OX-6+ cell localization. The intense expression of IL-1beta mRNA by periglomerular cells was demonstrated by in situ hybridization. CONCLUSIONS: The periglomerular distribution of OX-6+ED-1- DCs was demonstrated in anti-GBM crescentic GN in WKY rats. These DCs might be accumulated in periglomerular interstitium by CXCL12, and play a role in the initiation and progression of this GN by producing IL-1beta.
Authors: Christian Kurts; Felix Heymann; Veronika Lukacs-Kornek; Peter Boor; Jürgen Floege Journal: Semin Immunopathol Date: 2007-10-23 Impact factor: 9.623
Authors: Felix Heymann; Catherine Meyer-Schwesinger; Emma E Hamilton-Williams; Linda Hammerich; Ulf Panzer; Sylvia Kaden; Susan E Quaggin; Jürgen Floege; Hermann-Josef Gröne; Christian Kurts Journal: J Clin Invest Date: 2009-04-20 Impact factor: 14.808