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

Brown-Norway (BN) rats are uniquely susceptible to development of autoimmune phenomena and enlargement of lymph nodes and spleen after repeated injections of mercuric chloride. Despite its ability to produce autoimmunity, HgCl2 inhibited the development in BN rats of experimental allergic encephalomyelitis (EAE), another autoimmune process. The inhibition by mercury was probably due to lack of the normal absorption and granulomatous reaction to the EAE inoculum in the enlarged lymph nodes draining the inoculation site. Lewis rats did not develop enlarged nodes from HgCl2 treatment. Lewis lymph nodes absorbed the EAE inoculum abundantly and developed an extensive granulomatous reaction despite the mercury treatment, and there was only a slight inhibition of EAE. Therefore, the ability of HgCl2 to produce lymphadenopathy in BN rats may be responsible for the inability of these rats to absorb the inoculated antigen. The mercury-induced failure of absorption was manifested as an inhibition of EAE in BN rats.
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PMID:Suppression of experimental allergic encephalomyelitis in rats by mercuric chloride. 278 62

Mercuric chloride induces in Brown-Norway rats an autoimmune disease due to a T dependent polyclonal activation of B cells. Various autoantibodies and a striking increase in total serum IgE level are observed as consequences of this polyclonal activation. The aim of this study was to investigate the in vitro response of autologous syngeneic normal lymphocytes to lymphocytes exposed in vivo or in vitro to HgCL2. Helper/inducer T cells (W3/25 +) exposed to HgCl2 were found to stimulate normal T lymphocytes in the presence of normal Ia (+) cells. The proliferating T cells also had the helper/inducer phenotype. To demonstrate the potential relevance of this in vitro phenomenon to the autoimmune disease, HgCl2-pretreated T cells were injected into the footpads of normal syngeneic recipients. Draining popliteal lymph nodes contained a highly significant number of both surface IgE positive and IgE containing cells. These experiments demonstrate that HgCl2 induces autoreactive T cells and suggest that these cells may be responsible for the autoimmune disease.
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PMID:Autoreactive T cells in mercury-induced autoimmune disease: in vitro demonstration. 294 58

Brown-Norway (BN) rats injected with HgCl2 have been previously shown to develop a variety of autoimmune abnormalities. The susceptibility of BN rats is genetically controlled, and Lewis rats bearing a different RT1 haplotype are resistant. It will be shown in the present study that the number of MRC OX-8+ (suppressor/cytotoxic) cells increases in the spleen and lymph nodes of Lewis rats injected with HgCl2. The responsiveness to T cell mitogens and to alloantigens is concomitantly inhibited. Spleen cells from Lewis rats injected with HgCl2 fail to induce a local graft-vs.-host reaction. Data presented show that MRC OX-8+ cells are involved in the immunosuppression in Lewis rats treated with HgCl2. Furthermore, lymph node cells and MRC OX-8+ cells from these rats are able to inhibit the normal mixed lymphocyte reaction indicating that suppression is active. Thus, HgCl2 is able to trigger immune dysregulation leading either to autoimmunity or to immunosuppression depending upon the genetic background of the rat strain tested.
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PMID:HgCl2 induces nonspecific immunosuppression in Lewis rats. 294 85

Protein-loss into the gastrointestinal tract is a feature of many different diseases, a number of which are immunologically mediated, e.g. systemic lupus erythematosus or Crohn's disease. The pathogenic mechanism of protein-losing enteropathy in diseases without obvious enterocyte injury are unknown. Brown-Norway-rats (BN-rats) were gavaged with low doses of HgCl2 for 39 weeks. Within 2 weeks, the intestines showed strong linear staining for IgG and IgA along vascular and intestinal basement membranes. Granular deposits containing IgG and C3 were present along intestinal basement membrane only in the late stages of the experiment; only in these animals increased intestinal protein loss as measured by fecal Cr-51 excretion was found. These findings suggest that immune complex deposition along the intestinal basement membrane can lead to protein-losing enteropathy. This disease may be used as a model for the study of immunologically mediated intestinal disease.
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PMID:[Mercuric chloride-induced enteropathy in the rat: a model of gastrointestinal disease with immunologic pathogenesis]. 296 59

Mercuric chloride induces in Brown-Norway (BN) rats an autoimmune disease characterized by the production of various autoantibodies and by a marked increase in the IgE serum concentration. This agent is responsible for a T dependent polyclonal activation of B cells, which is probably due to the emergence of autoreactive T cells. The aim of this study was to evaluate the effect of HgCl2 injections on lymphoid organs and on the serum concentration of the various Ig isotypes. HgCl2 induced (1) a lymphoproliferation in spleen and lymph nodes involving B and T helper cells while the number of T suppressor/cytotoxic cells was not modified, (2) an increase in the number of Ig containing cells resulting in a rise in all serum Ig isotypes, and (3) an early thymic atrophy probably immunologically mediated, which was not involved in the induction phase of the disease since adult thymectomy had no effect. These findings demonstrate that the polyclonal effect of HgCl2 is not isotype-restricted although the IgE response is predominantly affected and they support evidence for a major role for an excess of T help in the HgCl2-induced polyclonal activation of B cells. It was also observed that B cell areas are present in normal BN rat thymuses, the potential role of which in the induction of autoimmunity remains to be investigated.
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PMID:HgC12 induces T and B cells to proliferate and differentiate in BN rats. 296 62

Mercuric chloride is responsible in Brown-Norway rats for an autoimmune disease that is autoregulated. Previous studies have shown that this agent induces T cell-dependent polyclonal B cell activation in these rats. Evidence has also been obtained for the existence of autoreactive T cells which play a role in the evolution of this process. In the present study, limiting dilution analysis was used to demonstrate that (a) frequent autoreactive T helper cells which proliferate in the presence of T cells from HgCl2-injected rats are present from day 4; (b) frequent auto-anti-Ia T helper cells which recognize normal B cells as well as B cells from HgCl2-injected rats appear from day 6; and (c) less frequent T suppressor cells which could play a role in autoregulation emerge from day 14.
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PMID:Autoreactive T cells in mercury-induced autoimmunity. Demonstration by limiting dilution analysis. 297 23

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

Mercury-induced autoimmunity in Brown-Norway rats has been shown previously to be due to polyclonal activation of B lymphocytes, requiring the presence of T lymphocytes. Autoimmunity in that strain is characterised by the appearance of an autoimmune glomerulonephritis, by the production of a host of autoantibodies, and by an increase in total serum IgE. In the present study, T-cell deprived rats were tested to assess the role of T cells in the appearance of autoimmune abnormalities in vivo. It will be shown that both BN rnu/rnu and BN 'B' rats, who have virtually no T cells, do not develop autoimmunity following HgCl2 injections. In contrast BN 'B' rats reconstituted with normal T cells, and BN rnu/+ rats, exhibit autoimmune manifestations, including autoimmune glomerulonephritis, quite similar to those observed in Brown-Norway rats. These data demonstrate that T cells are essential for mercury-induced autoimmunity to occur in Brown-Norway rats.
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PMID:Mercury-induced autoimmune glomerulonephritis: requirement for T-cells. 311 Jun 76

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

Mercuric chloride induces a transient systemic T-lymphocyte dependent autoimmune syndrome in Brown Norway rats. Two weeks after the first HgCl2 injection maximum serum levels of anti-GBM antibodies and nephrotic range proteinuria are detected. CyA treatment during HgCl2 administration completely prevented these autoimmune phenomena. Moreover, a prolonged unresponsiveness to HgCl2 was induced, lasting for at least 5 weeks after combined pretreatment with CyA and HgCl2. This unresponsiveness could not be adoptively transferred with peripheral lymphoid cells. Suppression of development of HgCl2-induced proteinuria was adoptively transferred with lymphoid cells from HgCl2-treated donors in remission phase. Unresponsiveness to HgCl2, induced by CyA plus HgCl2 pretreatment, could be broken by reconstitution with naive lymphoid cells. These results suggest that the tolerogenic effect of CyA in HgCl2-induced autoimmunity is not mediated by active suppression; instead, the observed unresponsiveness might be due to direct functional deletion of autoreactive T-lymphocytes. A serendipitous finding was the dissociation in time between synthesis of anti-GBM antibodies and development of proteinuria, suggesting a role for cellular effector mechanisms in the induction of proteinuria.
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PMID:Cyclosporin A induces long-term unresponsiveness in mercuric chloride-induced autoimmune glomerulonephritis. 318 May 13


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