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Article: Mercuric chloride-treated Brown Norway rats develop widespread tissue injury including necrotizing vasculitis

TitleMercuric chloride-treated Brown Norway rats develop widespread tissue injury including necrotizing vasculitis
Authors
Issue Date1992
Citation
Laboratory Investigation, 1992, v. 67 n. 1, p. 121-129 How to Cite?
AbstractBACKGROUND: Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown Norway (BN) rats, characterized by polyclonal B cell activation and circulating autoreactive T cells. A number of autoantibodies are produced, including antibodies to glomerular basement membrane, and there are circulating immune complexes. However, histologic evidence of tissue injury in this model has previously been reported to be rare. EXPERIMENTAL DESIGN: Six BN rats were given five injections of HgCl2, each of 1 mg/kg, over 10 days. Controls were four BN rats given equal volumes of saline and 10 Lewis rats given the same amount of HgCl2. Blood samples were taken thrice weekly. Animals were killed at various stages, necropsies performed, and organs histologically examined. The effect of pretreatment with broad spectrum antimicrobial drugs was examined by comparing two further groups of six BN rats: one group was pretreated with tylosin, ivermectin, and metronidazole before HgCl2 was given, and the other group received no pre- treatment. RESULTS: HgCl2-treated BN rats developed inflammation and ulceration of the skin which was most marked at mucocutaneous junctions. Macroscopic examination of internal organs showed hepatomegaly and gross haemorrhagic lesions in the wall of the gut, most marked in the duodenum and caecum. Microscopically, the skin lesions were characterized by a subepidermal mononuclear cell infiltrate with occasional hair shaft necrosis. In the liver there was a periportal mononuclear cell infiltrate, and in the gut there was intense submucosal inflammation and a leucocytoclastic vasculitis accompanied in places by mucosal ulceration. Lewis rats (which are not prone to mercury-induced autoimmunity) showed no such changes after receiving HgCl2, nor did control BN rats given saline. BN rats pretreated with broad spectrum antimicrobial agents and then given HgCl2 showed milder histologic abnormalities, although antimicrobial treatment did not affect the antiglomerular basement membrane autoantibody response. CONCLUSIONS: We have identified a syndrome induced by mercuric chloride in BN rats in which there is evidence of tissue injury in many organs, with some features in common with graft-versus-host disease. There is also necrotizing leucocytoclastic vasculitis affecting the gut, and the importance of this is enhanced by the description in the accompanying paper of autoantibodies similar to those found in human systemic vasculitis. Our observations strengthen the analogies between this model and human autoimmune disease.
Persistent Identifierhttp://hdl.handle.net/10722/195416
ISSN
2015 Impact Factor: 4.202
2015 SCImago Journal Rankings: 2.133
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMathieson, PW-
dc.contributor.authorThiru, S-
dc.contributor.authorOliveira, DBG-
dc.date.accessioned2014-02-28T06:12:07Z-
dc.date.available2014-02-28T06:12:07Z-
dc.date.issued1992-
dc.identifier.citationLaboratory Investigation, 1992, v. 67 n. 1, p. 121-129-
dc.identifier.issn0023-6837-
dc.identifier.urihttp://hdl.handle.net/10722/195416-
dc.description.abstractBACKGROUND: Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown Norway (BN) rats, characterized by polyclonal B cell activation and circulating autoreactive T cells. A number of autoantibodies are produced, including antibodies to glomerular basement membrane, and there are circulating immune complexes. However, histologic evidence of tissue injury in this model has previously been reported to be rare. EXPERIMENTAL DESIGN: Six BN rats were given five injections of HgCl2, each of 1 mg/kg, over 10 days. Controls were four BN rats given equal volumes of saline and 10 Lewis rats given the same amount of HgCl2. Blood samples were taken thrice weekly. Animals were killed at various stages, necropsies performed, and organs histologically examined. The effect of pretreatment with broad spectrum antimicrobial drugs was examined by comparing two further groups of six BN rats: one group was pretreated with tylosin, ivermectin, and metronidazole before HgCl2 was given, and the other group received no pre- treatment. RESULTS: HgCl2-treated BN rats developed inflammation and ulceration of the skin which was most marked at mucocutaneous junctions. Macroscopic examination of internal organs showed hepatomegaly and gross haemorrhagic lesions in the wall of the gut, most marked in the duodenum and caecum. Microscopically, the skin lesions were characterized by a subepidermal mononuclear cell infiltrate with occasional hair shaft necrosis. In the liver there was a periportal mononuclear cell infiltrate, and in the gut there was intense submucosal inflammation and a leucocytoclastic vasculitis accompanied in places by mucosal ulceration. Lewis rats (which are not prone to mercury-induced autoimmunity) showed no such changes after receiving HgCl2, nor did control BN rats given saline. BN rats pretreated with broad spectrum antimicrobial agents and then given HgCl2 showed milder histologic abnormalities, although antimicrobial treatment did not affect the antiglomerular basement membrane autoantibody response. CONCLUSIONS: We have identified a syndrome induced by mercuric chloride in BN rats in which there is evidence of tissue injury in many organs, with some features in common with graft-versus-host disease. There is also necrotizing leucocytoclastic vasculitis affecting the gut, and the importance of this is enhanced by the description in the accompanying paper of autoantibodies similar to those found in human systemic vasculitis. Our observations strengthen the analogies between this model and human autoimmune disease.-
dc.languageeng-
dc.relation.ispartofLaboratory Investigation-
dc.titleMercuric chloride-treated Brown Norway rats develop widespread tissue injury including necrotizing vasculitis-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid1625442-
dc.identifier.scopuseid_2-s2.0-0026734809-
dc.identifier.volume67-
dc.identifier.issue1-
dc.identifier.spage121-
dc.identifier.epage129-
dc.identifier.isiWOS:A1992JE25900012-

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