Podocyte expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1) in experimental pauci-immune crescentic glomerulonephritis

Abstract

SUMMARYWe examined immunopathological changes of podocytes in vivo which, based on in vitro studies, are thought to be relevant for the pathogenesis of renal diseases. We investigated the alterations of podocytes in local inflammation in a recently developed model of pauci-immune necrotizing crescentic glomerulonephritis (NCGN) in the rat. Frozen and plastic embedded kidney sections at different time points of the disease were incubated with antibodies directed to MHC class I, MHC class II, ICAM-1 and to relevant cytokines. Strong glomerular expression of MHC class I, II and ICAM-1 was found within 4 days, and plastic embedded sections clearly demonstrated increased cell membrane staining of podocytes. Increased glomerular interferon-gamma (IFN--y) was detected within 24 h of induction of NCGN, and IL-1,3 and tumour necrosis factor-alpha (TNF-a) were found from day 4. The potency of these cytokines to induce adhesion molecules on podocytes was investigated on rat glomerular epithelial cells in vitro. By using FACS analysis and electron microscopical techniques, we found that the in vivo expression of MHC class I, II and ICAM-l by podocytes could in vitro be simulated by IFN--y. IFN-a weakly induced MHC class I, while IL-lf and TNF-a were ineffective. We hypothesize that podocytes in this in vivo model are important to maintain the local inflammatory process in the glomerulus by expression of relevant adhesion molecules and MHC molecules upon stimulation with specific cytokines. Keywords glomerular visceral epithelial cells MHC intercellular adhesion molecule-l interferon-alpha interferon

Interferon-gamma (IFN-γ) and IL-4 expressed during mercury-induced membranous nephropathy are toxic for cultured podocytes

“…the 6-and the IL-4-supeniatant exerted similar aspecific toxic effects on macrophages //; vitro, as determined by trypan blue exclusioti. Titrationexperitnents revealed that MHC expression by IFN--r was found with a concentration of 100 U/ml [23]. as determined by others as well [24,25].…”

Renal participation of myeloperoxidase in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis

“…36 Alternatively, MPO can be directly transferred from neutrophils to endothelial cells in a β2-integrinmediated, cell-cell contact manner that may occur with little or no release of extracellular MPO. 37 As human glomerular endothelial cells and podocytes express major histocompatibility complex class II in inflammatory states, [38][39][40] internalized MPO may be processed and presented as peptides to autoreactive MPO-specific CD4+ T cells by intrinsic kidney cells. 41 Mesangial cells can also express major histocompatibility complex class II, but because of a lack of specific mesangial cell marker, we could not determine whether MPO localized to mesangial cells.…”

Transplant Glomerulopathy

“…Podocytes express MHC class I and class II molecules, and this increases under inflammatory conditions. 11,12 Furthermore, podocytes can serve as antigen-presenting cells, and deleting MHC class II exclusively on podocytes markedly attenuates the severity of GN in a mouse model of anti-GBM nephritis. 12 Yang et al 9 did not compare glomerulitis in their cases of early versus late TG, and they observed acute ABMR only infrequently before the development of early or late TG, although diagnosis was based on an older version of the Banff classification that did not recognize C4d-negative ABMR.…”