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

Only few reports are available on the consequences of chronic oral administration of low doses of mercuric chloride (HgCl2). Forty Brown-Norway rats received 150 micrograms HgCl2/100 g body weight 3 times a week by gavage or by i.m. injection with 100 micrograms twice per week. After 2 weeks of oral HgCl2 administration, the rats lost weight and hair. Phases of proteinuria were observed in weeks 5-8 and then continuously from week 12 until the end of the experiment at week 39. Antibodies binding to renal, intestinal, and vascular basement membrane developed after 2 weeks; circulating immune complexes were detectable in increasing titers starting at week 3. There were linear deposits of IgG, IgM, and IgA in the glomerular basement membrane and tubular basement membrane, and along the intestinal basement membrane. After week 11, the first granular immune deposits were observed in renal and intestinal basement membranes. Light microscopy showed thickening of glomerular basement membrane, mesangial matrix, and tubular basement membrane. In addition, interstitial nephritis was observed in some animals. Interestingly, kidney involvement was as severe in the orally as the i.m.-treated animals.
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PMID:Autoimmune disease induced by oral administration of mercuric chloride in Brown-Norway rats. 353 91

Brown Norway rats injected with mercuric chloride (HgCl2) develop autoantibodies which immunolocalize along the glomerular basement membrane at first in a linear pattern and then in a granular pattern. The aim of this study was to characterize the specificity of these antibodies and to investigate the mechanisms responsible for the formation of granular immune deposits in the subepithelial zone of the glomerular basement membrane. The rats were found to develop circulating anti-laminin, anti-type IV collagen, anti-heparan sulfate proteoglycan, and anti-entactin antibodies. Antibodies against laminin and type IV collagen were found in relatively high titers in the sera and were specifically concentrated in the nephritic kidneys. Antibodies eluted from the nephritic kidneys with either linear or granular deposits reacted with basement membrane antigens synthesized and secreted by cultured rat glomerular visceral epithelial cells. Thus, in this model, the interaction of anti-laminin and type IV collagen antibodies with antigens secreted by glomerular visceral epithelial cells might, together with other mechanisms, contribute to the formation of granular immune deposits in the subepithelial part of the glomerular basement membrane.
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PMID:Studies on the formation of glomerular immune deposits in brown Norway rats injected with mercuric chloride. 362 83

The effect of neonatal IgE injections on total IgE responses was studied in two rat models. After Nippostrongylus brasiliensis infection, no differences in serum IgE level and surface or cytoplasmic IgE expression were observed between IgE-treated and control LOU/C rats. Likewise, after HgCl2 injection, IgE-treated Brown-Norway rats and controls showed no difference in serum IgE level or in the development of autoimmune glomerulonephritis and proteinuria. It has been concluded that IgE-class-restricted tolerance, induced by neonatal injections of IgE, cannot be observed in rats after strong IgE stimulation.
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PMID:Neonatal IgE injections do not modify Nippostrongylus brasiliensis-induced and mercuric chloride-induced IgE increase in the rat. 380 64

Mercuric chloride induces in Brown-Norway rats a polyclonal activation of B cells resulting in a lymphoproliferation and in the production of autoantibodies. Experiments were performed to test the role of cells modified by HgCl2 in the induction of B cell proliferation by using the popliteal lymph node assay. Spleen cells, T cells and peritoneal macrophages exposed in vivo or in vitro to HgCl2 induced a proliferation of T and B cells in the draining popliteal lymph node. Spleen cells from Lewis rats who received HgCl2 were ineffective. These data suggest that modified cells could trigger autologous lymphocyte subsets and be responsible for autoimmunity induced by HgCl2.
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PMID:In vivo self-reactivity of mononuclear cells to T cells and macrophages exposed to HgCl2. 387 39

Mercuric chloride induces in the Brown-Norway rat a biphasic autoimmune disease characterized initially by linear IgG deposits along the glomerular basement membrane followed later by granular IgG deposition. In the present study, anti-glomerular basement membrane antibodies and immune complex-like material were sequentially assessed in serial serum samples. Both were transiently found at the same period. Glomerular linear IgG deposits were present on day 11 but circulating anti-glomerular basement membrane antibodies were only found later on day 16. Circulating immune complexes were first detectable on day 8 before the earliest granular IgG deposits were first observed in the spleen vessels on day 16. The disappearance of circulating anti-glomerular basement membrane antibodies and of circulating immune complexes, although HgCl2 injections were pursued, is in agreement with the self-limited character of mercuric chloride induced autoimmune disease and suggests the induction of immunosuppressive mechanisms.
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PMID:Mercuric chloride induced autoimmune disease in Brown-Norway rats: sequential search for anti-basement membrane antibodies and circulating immune complexes. 621 54

Mercuric chloride induces a biphasic autoimmune glomerulonephritis in Brown-Norway (BN) rats but not in Lewis (LEW) rats. The genetic control of susceptibility to both phases was investigated by testing the response of segregants between BN and LEW rats and of congenic LEW.1N rats. It was confirmed that susceptibility to the first phase, characterized by the appearance of anti-glomerular basement membrane antibodies, depends on several genes one of which is RT1 linked. Susceptibility to the second phase, which is an immune complex type glomerulonephritis, was found to depend on one major RT1 linked gene or cluster of genes with a role for other(s) non-RT1 linked gene(s) controlling the magnitude of the response. However, congenic LEW.1N rats were found to be resistant. This suggests that the disease gene has been lost during the strain derivation. The question of whether both phases are two different diseases or expression of the same process cannot be definitely answered; data however indicate a dissociation of both disease processes.
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PMID:Immune complex type disease induced by HgCl2 in Brown-Norway rats: genetic control of susceptibility. 621 44

Mercuric chloride induces an autoimmune glomerulonephritis in Brown-Norway (BN) but not in Lewis (LEW) rats. Injection of HGCl2 into BN rats regularly produced a transient appearance of plaque-forming cells (PFC) of anti-2,4,6-trinitrophenyl and anti-sheep red blood cell specificity and circulating anti-single-stranded DNA antibodies. Addition of HgCl2 to spleen cell cultures from BN rats induced an increase in anti-trinitrophenyl PFC and reverse PFC. This effect was no longer observed when nylon wool column-depleted or anti-Thy-1 antiserum-treated spleen cells were cultured in the presence of HgCl1. These data suggest that HgCl2 acts as a polyclonal activator on spleen cells in BN rats, but not on isolated B lymphocytes. In contrast, no effect of HgCl2 on immunoglobulin production was observed in LEW rats. Since polyclonal activation and immune-type nephritis are both seen in BN but not in LEW rats, polyclonal activation may participate in the pathogenesis of the HgCl2-induced autoimmune disease of BN rats.
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PMID:Polyclonal effect of HgCl2 in the rat, its possible role in an experimental autoimmune disease. 621 11

Brown-Norway (BN) rats are susceptible to the induction of an autoimmune glomerulonephritis (GN) by HgCl2 while Lewis (LEW) rats are resistant. When a kidney from a LEW rat (nonsusceptible) is transplanted into a binephrectomized (LEW X BN)F1 hybrid (susceptible) then HgCl2 injections into the recipient result in GN developing in the donor kidney. When a kidney from a BN or (LEW X BN)F1 hybrid (susceptible) is transplanted into a nonsusceptible rat, injections of HgCl2 into the recipient do not result in GN in the donor kidney. These observations show that kidneys from nonsusceptible rats function as susceptible targets and that induction of the disease depends more on the host immune system than on modification of kidney determinants by HgCl2.
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PMID:Mercuric chloride nephritis depends on host rather than kidney strain. 622 17

The respective roles of circulating anti-glomerular basement membrane antibodies and of circulating immune complexes in the appearance of glomerular linear and granular IgG deposition during HgCl2-induced glomerulonephritis in the Brown-Norway rat has been studied. Syngeneic kidney transplantations have been performed at various phases of the disease. Results show that circulating antibodies are responsible for linear IgG deposition which did not change to granular deposits during the course of the disease. Electron-dense subepithelial deposits occurred only when circulating immune complexes were detected. These experiments strongly suggest that, in the mercury model, circulating immune complexes are responsible for granular IgG deposits observed in arteries and in the subepithelial space of glomeruli.
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PMID:Glomerular and vascular IgG deposits in HgCl2 nephritis: role of circulating antibodies and of immune complexes. 622 64

The effects of cyclophosphamide on autoantibody synthesis were studied in an experimental model of glomerulonephritis due to autoantibodies to the glomerular basement membrane (GBM). Brown Norway rats develop anti-GBM antibodies, as part of a polyclonal response, when repeatedly injected with mercuric chloride (HgCl2). Anti-GBM antibody levels peak between days 11 and 14 and thereafter rapidly fall; convalescent animals show a time-dependent resistance to rechallenge with HgCl2 which remains significant for up to 3 months. The administration of cyclophosphamide, as a single intramuscular injection at day 0, has three distinct dose-dependent effects on anti-GBM antibody production. Firstly, lower doses (2.5 mg/kg) increase antibody levels at the time of peak response; secondly, higher doses (greater than or equal to 20 mg/kg) prevent antibody synthesis following HgCl2; and thirdly, the higher doses also reduce the response to rechallenge with HgCl2 3-4 months later. These effects of cyclophosphamide also apply to the polyclonal response to HgCl2, as judged by measurement of total IgG concentrations. Further investigation of the mechanisms of action of cyclophosphamide in this model should provide information relevant to the treatment of human autoimmune disease.
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PMID:Effects of cyclophosphamide on autoantibody synthesis in the Brown Norway rat. 622 57


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