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E Druet

Publications and source records attributed to E Druet.

33 records · Page 2Linked to original sources

Mercuric chloride induced autoimmune disease in Brown-Norway rats: sequential search for anti-basement membrane antibodies and circulating immune complexes.

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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Immune complex type disease induced by HgCl2 in Brown-Norway rats: genetic control of susceptibility.

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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Immune-type glomerulonephritis induced in the Brown-Norway rat with mercury-containing pharmaceutical products.

It has been shown that Brown-Norway rats develop an immune-type glomerulonephritis after treatment with various mercury-containing drugs. Anti-GBM antibodies were involved, at least in some animals. This glomerulonephritis induced a proteinuria. Strong evidence is given, suggesting that most mercury compounds, some of which, such as mercurial antiseptics, are widely used, could induce an immune-type glomerulonephritis. The question therefore arises, whether these drugs can be used any longer.

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Extrarenal immune complex type deposits induced by mercuric chloride in the Brown Norway rat.

It has been reported previously that HgCl2 chronically injected in the BN rat induced a biphasic renal disease. During the first stage, anti-glomerular basement membrane antibodies appeared and during the second stage, an immune-complex type glomerulonephritis was observed. In the present study, a systemic immune disease is described. During the first stage, antibasement membrane antibodies were observed in various extrarenal structures. Their localization has been found to depend mainly on the characteristics of the endothelium. During the second stage, immune-complex type deposits containing IgG and C3 were found in most vascular structures. Their localization did not apparently depend on the endothelial characteristics. Among the organs tested the lung was most often spared. The occurrence of immune complex deposits was found to depend on the dose of HgCl2 injected: deposits were absent in some high dose HgCl2-injected rats but they were very numerous in low dose HgCl2-injected rats. These deposits probably have a pthogenic role although no major histological lesion could be found. This model may help to explain immune complex type deposits in systemic diseases.

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Mercuric chloride-induced anti-glomerular basement membrane antibodies in the rat: genetic control.

Mercuric chloride induces anti-glomerular basement membrane antibodies in the Brown-Norway rat. Various other inbred rat strains (Lewis, Wistar AG, August, PVG/c) were not found to be able to produce such antibodies under the same experimental conditions. Hybrids (F1, F2 and F1 x LEW) were bred from Brown-Norway and Lewis rats and injected with mercuric chloride. It has been demonstrated that the induction of anti-glomerular basement membrane antibodies by mercuric chloride in these crosses is under genetic control. The response was found to depend on two or three genes one of which was H-1-linked. The negative results obtained with L.BN congenic rats were in complete agreement with this conclusion.

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Induction of anti-glomerular basement membrane antibodies in the Brown-Norway rat by mercuric chloride.

Anti-glomerular basement membrane (GBM) antibodies were induced in the Brown-Norway rat by mercuric chloride. The existence of anti-GBM antibodies was suspected because of the immunofluorescent linear pattern. It was proved because eluted antibodies from kidneys and circulating IgG had an anti-glomerular basement membrane activity. A glomerular basement membrane antigen modified by HgCl2 is probably responsible for the appearance of such antibodies. The previous demonstration of the occurrence of an immun complex type glomerulonephitis, in outbred Wistar rats, under the same experimental conditions, suggests the existence of a genetic control for this type of immune response.

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[Induction of anti-glomerular basement membrane antibodies in BN rats: genetic control].

Mercuric chloride induces anti-glomerular basement membrane antibodies in Brown Norway rats (Ag B3) and not in Lewis rats (Ag B1). Studies on (Lewis X BN) F1 and F2 and with back-crosses (Lewis X BN) F1 X Lewis demonstrate a genetic control for this immune response. This genetic control probably depends on two non-linked, autosomal and dominant genes. One of these genes is linked to the major histocompatibility locus.

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Complement studies in BN rats with mercuric chloride-induced immune glomerulonephritis.

Whole complement haemolytic activity (CH50) changes were examined in 71 rats, developing and HgCl2-induced biphasic immune glomerulonephritis. In some rats, serum C4 level was also studied. Whole CH50 level was compared with proteinuria and C3 glomerular deposits. In control rats or in rats injected with low doses of HgCl2, there was no complement decrease. In rats injected with a high dose, after an initial increase (also observed in controls), CH50 level decreased between day 12 and day 20, sometimes dramatically. This decrease, observed during the first phase, was transient, CH50 levels returning to normal before day 30. Serum C4 level varied in accordance with CH50, indicating a classical pathway activation of complement. Fall in CH 50 and proteinuria was correlated: the heavier the proteinuria, the greater the fall in complement (p < 0.01). Whether proteinuria is or is not the consequence of the complement activation, remains to be demonstrated.

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Immune type glomerulonephritis induced by HgCl2 in the Brown Norway rat.

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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