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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of autoimmune antibodies against antigens of glomerular basement membrane (GBM) was studied in nine inbred strains of rats each with a different major histocompatibility complex H-1. Brown-Norway (BN) (H-1n), Lewis (H-1(1)), PVG/c (H-1c), AS2 (H-1f), AVN (H-1a), BD V (H-1d), DA (H-1a) and F344 (H-1(1)) rats were immunized with bovine GBM and Freund's complete adjuvent (CFA). A pronounced linear deposition of host IgG (IgG1 and IgG2a) along the GBM was found in BN rats. No deposition of C3 could be detected in the glomeruli nor did the animals develop proteinuria. The quantity of autoimmune antibodies fixed to the GBM was low (48 microgram +/- 14) which could explain the absence of C3 deposition and proteinuria. The antigenic specificity of the antibodies deposited along the GBM in BN rats was shown by the fixation in vitro of the eluted antibodies to the GBM and tubular basement membrane (TBM) of normal kidneys. A much weaker and irregular deposition of host IgG along the GBM was observed in PVG/c, AS2. AVN, BD V, DA and F344 rats. Of these strains, eluates from the glomeruli of PVG/c, AVN, BD V and DA rats fixed very weakly to the GBM of normal kidneys whereas eluates from AS2 and F344 rats did not fix to GBM or TBM. No deposition of host IgG was found in Lewis rats, and the eluates did not fix to normal kidneys. Congenic L.BN rats with the BN H-1n haplotype and a Lewis background did not respond. This study shows a genetic predisposition in rats to an autoimmune anti-GBM response which is not, or not exclusively, controlled by genes linked to the H-1 histo-compatibility complex.
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PMID:Induction of autoimmunity to antigens of the glomerular basement membrane in inbred Brown-Norway rats. 37 60

HgCl2 chronically injected in the Brown-Norway rat induced a biphasic renal disease. The first stage was characterized by anti-glomerular basement membrane antibodies. The second stage by the appearance of immune complexe type deposits in the glomerular tufts and in the small renal arteries. These immune complexes were constituted of a basement membrane component and anti-basement membrane antibodies. Other immune complexes were perhaps involved. In most of the rats, a proteinuria and a nephrotic syndrome appeared, as a consequence of this immune disease. No abnormalities were observed in Lewis rats, suggesting a role for a genetic control of this immune response.
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PMID:Immune type glomerulonephritis induced by HgCl2 in the Brown Norway rat. 74 85

To study immune reactive and thrombotic mechanisms involved in chronic renal allograft rejection, Lewis rat kidneys were transplanted into bilaterally nephrectomized Brown Norway recipients tolerant of LEW erythrocyte antigens. Such BN rats fail to produce anti class I MHC alloantibodies after insertion of a LEW kidney. The LEW renal allografts experience a transient rejection episode without proteinuria followed by the development of chronic rejection, clinically characterized by glomerular proteinuria in the presence of stable renal function. Immunohistological studies of such chronically rejected LEW renal allografts showed the occurrence of glomerular and interstitial infiltration of predominantly monocytes and T cells. CD4-positive T cells dominated over CD8-positive T cells in the chronically rejected LEW renal grafts. IgG deposition was found deposited throughout the renal vasculature--this in contrast to IgM, which was observed only in the glomerular vasculature. Glomerular antibodies were not directed to endothelial class II MHC antigens, and showed only weak complement fixation as demonstrated by C3 staining. Selective glomerular IgM deposition was associated with vascular (platelet-containing) thrombi, and focal and segmental fibrinoid necrosis. In contrast, acutely rejected LEW renal grafts in unmodified BN recipients showed IgM deposition as well as thrombus formation throughout the entire renal vasculature. The results demonstrate that the antibody response to endothelial--and, in particular, glomerular endothelial non-MHC antigens--may bring about chronic vascular renal allograft rejection. How the formation of glomerular thrombotic lesions may be assisted by endothelial reactivity to cytokines from local immune reactive cells is discussed.
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PMID:Chronic renal allograft rejection. Selective involvement of the glomerular endothelium in humoral immune reactivity and intravascular coagulation. 187 89

Mercuric chloride (HgCl2) induces in Brown Norway rats a CD4+ T lymphocyte-dependent systemic autoimmune syndrome, involving synthesis of anti-glomerular basement membrane autoantibodies and development of proteinuria. Lewis rats are resistant to HgCl2-induced autoantibody production and, in contrast, develop immunosuppression, mediated by CD8+ T lymphocytes. In the present study, genetic requirements governing autoreactivity or immunosuppression in response to HgCl2 were further explored. Both major histocompatibility complex (MHC) and non-MHC genes are involved in determining susceptibility to HgCl2-induced autoimmunity. Both AO (RT1u) and DZB (RT1u) rats were found to develop a membranous autoimmune glomerulopathy upon exposure to HgCl2. Only the DZB strain, which differs in part of the non-MHC background from AO, developed proteinuria. AO.1P (RT1.AuB1D1Eu) rats, which are genetically identical to AO except for the Lewis haplotype at the MHC class II loci, appeared to develop immunosuppression upon exposure to HgCl2. It is concluded that autoreactivity and immunosuppression, induced by HgCl2, are both dependent on the MHC class II haplotype. In autoimmune responder strains the type of autoimmune glomerulopathy is influenced by non-MHC genes.
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PMID:Susceptibility to the induction of either autoimmunity or immunosuppression by mercuric chloride is related to the major histocompatibility complex class II haplotype. 200 8

Administration of HgCl2 to the susceptible Brown-Norway (BN) strain of rats induces an autoimmune disease characterized by polyclonal B cell activation, increased serum levels of IgE and the occurrence of anti-glomerular basement membrane antibody-mediated glomerulonephritis. We have observed that the simultaneous administration to BN rats of normal human polyspecific immunoglobulins for therapeutic use (IVIg) with HgCl2 significantly decreased the occurrence and severity of proteinuria, and reduced serum IgE levels in diseased animals. Hypergammaglobulinaemia was potentiated in animals receiving HgCl2 and IVIg, compared with animals receiving HgCl2 alone. In vitro experiments indicated that F(ab')2 fragments from IVIg inhibited the binding to laminin of pathogenic anti-laminin antibodies from diseased rats, as did antibodies from the resistant Lewis strain of rats but not antibodies from susceptible BN rats. These observations suggest that IVIg may interfere with the immune regulatory mechanisms involved in mercury-induced autoimmune disease in an analogous fashion to the ability of IVIg to suppress the expression of certain pathological autoimmune responses in humans.
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PMID:Beneficial effect of human therapeutic intravenous immunoglobulins (IVIg) in mercuric-chloride-induced autoimmune disease of Brown-Norway rats. 201 3

In Brown-Norway (BN) rats mercuric chloride induces an autoimmune disease characterized by an increase in serum IgE concentration, and by the production of anti-glomerular basement membrane antibodies responsible for a glomerulonephritis with a heavy proteinuria. (i) This disease results from a B-cell polyclonal activation probably due to frequent anti-class II T cells. (ii) The self limitation observed in this model is associated with both a decrease in the frequency of anti-class II T cells and the emergence of CD8+ T cells able to suppress these autoreactive T cells. (iii) In Lewis (LEW) rats which do not develop autoimmunity, HgCl2 provokes the appearance of non-antigen-specific CD8+ T cells responsible for a depression of T-cell functions. The aim of this work was to test the effect of treatment with an anti-CD8 monoclonal antibody (MoAb) in both BN and LEW rats. Anti-CD8 MoAb-treated rats were effectively depleted in CD8+ T cells. However, neither the induction nor regulation phases of mercury-induced autoimmunity were modified in BN rats. Mercury-induced immunosuppression in LEW rats was abrogated; however, depletion in CD8+ T cells did not allow the disease to occur in that strain. Finally, CD8 depletion induced in normal BN rats the appearance of rare anti-class II T cells showing that these cells are normally present in that strain but negatively controlled by suppressor T cells.
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PMID:Role of CD8+ T cells in mercury-induced autoimmunity or immunosuppression in the rat. 213 55

A 38-year old patient had been suffering, since the age of 17, from membranoproliferative glomerulonephritis associated with chronic atopic eczema and recurrent sinusitis. Bouts of eczema with severe itching occurred simultaneously with sinusitis and proteinuria. Permanently extreme serum IgE levels (greater than 10,000 IU/ml), defective neutrophil chemotaxis and monocyte phagocytic function (Buckley's syndrome) were present. Because cyclosporin reduces excessive IgE levels in Brown Norway rats with mercuric chloride nephritis, we gave the patient this drug in daily doses of 3-4 mg/kg. A dramatic improvement resulted within a few days: itching disappeared, the eczema progressively cleared, proteinuria decreased to less than 0.5 g/day and serum IgE levels to 4000 KIU/l. Reduction of dosage was followed by recurrence of all clinical and biological signs. In spite of the improvement obtained, serum creatinine levels, which were initially high (200-250 mumol/l) rose up to 300 mumol/l after one year of treatment.
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PMID:[Membranoproliferative glomerulonephritis associated with Buckley's syndrome treated with cyclosporin]. 295 74

HgCl2 induces an autoimmune syndrome in Brown Norway rats that involves synthesis of anti-glomerular basement membrane (GBM) antibodies and development of nephritis with high proteinuria. HgCl2-induced changes in the composition of leukocyte populations and in the expression of MHC antigens in lymphoid and nonlymphoid organs were investigated by flow cytometry and immunohistochemistry. An early increase of CD4+ splenocytes was followed by a transient proliferation of CD4+ as well as CD8+ and B lymphocytes in peripheral lymphoid organs; in contrast, progressive depletion of the thymic cortex was found. B lymphocyte activation involved mainly the IgG1 and IgE isotypes. Nonlymphoid organs were infiltrated by MHC class II antigen expressing CD4+ and CD8+ T lymphocytes and monocytes; secondary to infiltration, mainly epithelial cells, being the main target of infiltrating cells, showed increased expression of MHC antigens. In glomeruli a 2.7-fold increase of CD8+ lymphocytes occurred after HgCl2-administration. The diverse autoimmune phenomena observed in this study fit with the hypothesized involvement of T lymphocytes autoreactive with MHC class II antigens. Apart from anti-GBM autoantibodies, a role for autoreactive CD8+ T lymphocytes must be considered in the pathogenesis of the HgCl2-induced autoimmune syndrome.
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PMID:Mercuric chloride-induced autoimmunity in the brown Norway rat. Cellular kinetics and major histocompatibility complex antigen expression. 305 91

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.
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PMID:Effect of methylprednisolone and cyclophosphamide in mercury-induced autoimmune glomerulonephritis. 311 Jun 91

Using an original technique permitting repeated plasma exchange in the rat, we have tested this therapeutic approach in animals actively immunised with horseradish peroxidase, and in rats with HgCl2-induced autoimmune glomerulonephritis. Plasma exchange effectively removes circulating IgG anti-horseradish peroxidase antibodies from the sera of immunised rats. When applied to the model of HgCl2-induced antiglomerular basement membrane glomerulonephritis in Brown-Norway rats, this technique is also remarkably effective. In these rats, proteinuria is abolished during the plasma exchange treatment period and no circulating antiglomerular basement membrane antibodies can be detected. These antibodies are, however, found in the ultrafiltrates of exchanged rats. Serum IgE, characteristically elevated in HgCl2-treated rats, is also markedly diminished in exchanged rats. Control rats treated with infusions of fresh frozen plasma or with heparin alone did not show any improvement in disease severity. These results suggest that plasma exchange alone can attenuate antiglomerular basement membrane nephritis in HgCl2-treated rats. This observation may be of relevance for the treatment of human antiglomerular-basement membrane-mediated glomerulonephritis.
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PMID:Plasma exchange in a rat model of autoimmune glomerulonephritis. 314 Jan 25


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