PODOCYTE EXPRESSION OF MHC CLASS-I AND CLASS-II AND INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) IN EXPERIMENTAL PAUCI-IMMUNE CRESCENTIC GLOMERULONEPHRITIS

We examined immunopathological changes of podocytes in vivo which, bas ed on in vitro studies, are thought to be relevant for the pathogenesi s of renal diseases. We investigated the alterations of podocytes in l ocal inflammation in a recently developed model of pauci-immune necrot izing crescentic glomerulonephritis (NCGN) in the rat. Frozen and plas tic embedded kidney sections at different time points of the disease w ere incubated with antibodies directed to MHC class I, MHC class II, I CAM-1 and to relevant cytokines. Strong glomerular expression of MHC c lass I, II and ICAM-1 was found within 4 days, and plastic embedded se ctions clearly demonstrated increased cell membrane staining of podocy tes. Increased glomerular interferon-gamma (IFN-gamma) was detected wi thin 24 h of induction of NCGN, and IL-1 beta and tumour necrosis fact or-alpha (TNF-alpha) were found from day 4. The potency of these cytok ines to induce adhesion molecules on podocytes was investigated on rat glomerular epithelial cells in vitro. By using FACS analysis and elec tron microscopical techniques, we found that the in vivo expression of MHC class I, II and ICAM-1 by podocytes could in vitro be simulated b y IFN-gamma. IFN-alpha weakly induced MHC class I, while IL-1 beta and TNF-alpha 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 m olecules upon stimulation with specific cytokines.