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Study of normotensive male Wistar/Rij rats indicates that some age-related changes include fixed systemic blood pressure, enhanced intrarenal vascular resistance and a corresponding step-wise reduction in renal blood flow and glomerular filtration rate per kidney weight. The morphological changes that occur include glomerular hypertrophy, glomerular basement thickening and reduced capillary surface.

Gene electrotranfer is an attractive physical method to deliver genes to target tissues. The aim of this study was to evaluate in vivo gene electrotransfer into spleen, one of the most important lymphoid organ, in order to create a new tool to modulate the immuno-inflammatory system. C57BI/6 mice were submitted either to intramuscular electrotransfer (IME) as a reference method or to intrasplenic (ISE) gene electrotransfer. In the naked injected plasmids, the CMV promoter controlled the expression of luciferase, secreted alkaline phosphatase, EGFP, or IFNγ. The ISE optimal electrotransfer conditions were first determined and ISE was found to be an efficient gene transfer method, which can be used to express secreted or intracellular proteins transiently. Although transfected cells were still present in the spleen 30 days after ISE, transfected spleen cells could recirculate since they were detected in extrasplenic locations. Using a Tlymphocyte-specific promoter controlling the expression of EGFP, splenic T cells could be targeted. Finally, it appeared that ISE procedure does not impair by itself the immune response and does not result in a significant production of antibodies directed to the transgenic proteins in C57BI/6 mice. This strategy constitutes a new method to manipulate the immune response that can be used in various experimental designs. [ABSTRACT FROM AUTHOR]

An IgG2a monoclonal antibody (MoAb) reacting with the brush border of the renal proximal tubule and glomerular capillary wall was produced by fusion of NSl myeloma cells with spleen cells from BALB/c mice immunized with renal brush border preparations from rat kidney cortex. This antibody reacts with a 90,000 mol. wt protein which can be isolated by immunoprecipitation of radiolabelled brush border or glomerular preparations and localized on these structures by immunoperoxidase electron microscopy, thus demonstrating the presence of common antigenic determinants. Survey of various organs showed that the MoAb reacted with the brush border of the gut, but also with antigens associated with the distal vascular system, in the liver antigenic determinants were located along the sinusoid walls but mainly on bile canaliculi. Specific glomerular binding could be demonstrated in vivo by immunofluorescence after an intravenous injection of 2 mg of antibody or by paired label methodology using tracer amounts. Kinetics however were dramatically different from those observed in classical passive Heymann nephritis since glomerular binding was transient during the first hours after injection. Binding was also found in tubular structures, as well as in lung, liver, spleen and heart. These results identify a well defined antigen antibody system responsible for the formation of transient extramembranous glomerular deposits and may be relevant to some human cases of glomerulonephritis. They may also provide new models to study glomerular and tubular transfer of membrane bound antibodies. [ABSTRACT FROM AUTHOR]

The distribution pattern of the C receptor (CR1) antigen, one of the earliest differentiation markers of the podocyte plasma membrane, has been studied during human renal ontogenesis by indirect immunofluorescence and immunoelectronmicroscopy using Fab'2 fragments ofanti-CR1 antibodies. CR1 antigen has been detected at the open-stage glomerulus, which precedes constriction of the vascular pole, along the capillary wall, in a thick and homogeneous pattern of staining. By immunoelectronmicroscopy, CR1 antigen was present on the porocyte plasma membrane towards the glomerular basement membrane (GBM), and diffusely distributed within the GBM according to a decreasing intensity gradient from podocytes to endothelial cells. At a later stage of differentiation (‘closed’ glomerulus stage) when constriction of the vascular pole has occurred, the podocyte plasma membrane appeared diffusely labelled for CR1;the GBM was also stained with a decreasing intensity gradient from podocytes to endothelial cells. This result indicates that a plasma membrane receptor belonging to the cell coat of podocytes can be found in the extracellular space within the GBM. Thus the antigenic repertoire of the GBM of human fetal kidney comprises antigens of constituent molecules of the extracellular matrix and planted antigens originating from adjacent cells. [ABSTRACT FROM PUBLISHER]

The effects of methylprednisolone and of cyclophosphamide were tested in mercury-induced autoimmune disease in Brown–Norway rats. Survival, proteinuria, presence of antiglomerular basement membrane bound antibodies and of immune complex type deposits, amounts of circulating immune complexes, and total serum IgE were studied. Serum IgE represents the most sensitive marker in this drug-induced autoimmune disease. Methylprednisolone alone (1.5 mg/kg per day) affected the course of the disease only slightly. Cyclophosphamide (20 mg/kg every other day) given from day 0 completely prevented all the autoimmune manifestations, but the rats were profoundly immunosuppressed. The same protective effect was obtained with lower cyclophosphamide dosage (15 mg/kg on day 0 and then 2 mg/kg per day). More interestingly, cyclophosphamide given from day 10 or 15 (20 mg/kg twice a week or every other day), at a time when the disease was already expressed, resulted in partial or complete recovery, provided that the rats had not exhibited heavy proteinuria before initiation of treatment. Cyclophosphamide is therefore a powerful agent, able to prevent and even to reduce the consequences of polyclonal activation in this model. [ABSTRACT FROM PUBLISHER]