In cadaveric organ transplantation there is a risk of transfer of infectious agents from donor to recipient. The consequences can be fatal for immunosuppressed recipients. This is illustrated by a case history in which an infection with the fungus Monosporium apiospermum was transferred from a donor to two cadaveric kidney recipients, of whom one died and the other survived with the loss of the graft. These events led to a review of the literature to determine methods of demonstrating possible contamination of donor organs. Analysis of the case history of potential donors, a history taken from relatives or the family doctor, autopsy and laboratory examinations are considered useful. Victims of drowning, patients with severe burns and patients who have been ventilated for a long time are high risk donors.
It has become apparent that extracellular matrix components and their cellular receptors, the integrins, are important regulators of glomerular development and function. In this rapidly evolving field we studied the production of extracellular matrix components and integrins by rat glomerular visceral epithelial and mesangial cells, using molecular probes and antibodies that have recently become available. Special attention was paid to laminin isoforms and to splice variants of the integrin subunits a 3 and a6. Results were compared to the in vivo expression in human fetal, newborn and adult kidneys. The mesangial cells were found to produce laminin-1, nidogen and two as yet unidentified laminin isoforms with putative (Y chains of about 395 (m) and of 375 kDa (cry), tentatively described before as bovine kidney laminin. Furthermore, they expressed the integrins d p l , cu2p1, a3Ap1, a5p1, cwp3, mp5, and small amounts of d A p l and a6Bpl. The glomerular visceral epithelial cells produced the two new laminin isoforms mentioned above, laminin-5, but no laminin-1 or nidogen. The integrins (~2p1, (~3Ap1, &Am, a 6 B P and the integrin subunit av were found to be expressed. We show that during nephrogenesis, the laminin a 1 chain disappears and is replaced by another (Y chain, possibly one of the two as yet unidentified (Y chains mentioned above. The laminin pl chain is replaced by the p2 chain somewhat later in glomerular development. In general, the integrins found to be expressed in glomeruli of adult kidney were consistent with those found in cultured glomerular visceral epithelial and mesangial cells. No splice variant switch of the integrin a 3 or a6 subunits could be demonstrated during nephrogenesis.Our results suggest an important role for the mesangial cell in providing nidogen as a crucial component of the supramolecular stucture of the glomerular basement membrane. Furthermore our results indicate that laminin axp2yl and ayp2yl isoforms are important in the glomerulus of adult kidney and that the integrin a3Apl is the main integrin receptor for laminin isoforms on glomerular visceral epithelial and mesangial cells, both in vitro and in vivo.
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
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