Lupus-like oral mucosal lesions in mercury-induced autoimmune response in Brown Norway rats

Abstract

BackgroundAdministration of mercury at nontoxic doses induces systemic autoimmune disease in Brown Norway (BN) rats. The pathogenesis of lupus-like oral mucosal lesion by mercury-induced autoimmunity is still unclear, even though the oral mucosa is observed to be commonly affected in mercury-treated BN rats. In this study, we investigated the immunopathology of lupus-like oral mucosal lesions in a model of mercury-induced systemic autoimmunity.MethodsBrown Norway male rats were injected subcutaneously with either phosphate-buffered saline (control) or mercury at a dose of 1.0 mg per kilogram of body weight on days 0, 3, 5, and 7. Blood, kidney, and tongue samples were taken at various timepoints for evaluation by immunohistochemistry, RT-PCR, and lupus band test (LBT).ResultsOral mucosal lesions were classified according to three consecutive temporal phases on the basis of infiltration of immunocompetent cells as follows: (phase I) infiltration of MHC class II+ dendritic cells (DC) and macrophages; (phase II) addition of ED1+ macrophage infiltrates; and (phase III) focal infiltration of pan T cells following increased infiltration of DC and macrophages. Dense infiltration of DC and macrophages was observed in the basement membrane (BM) zone of the oral epithelium. Tissue expression of IL-4 mRNA was detected in early lesions (phase I), suggesting that locally produced IL-4 may be responsible for Th2-mediated immune response. A linear and continuous smooth pattern of fluorescence was observed in the oral epithelial BM in addition to renal glomeruli, indicating immune complex deposits.ConclusionsLocal autoimmune responses are involved in the pathogenesis of mercury-induced lupus-like lesions of the oral mucosa.

Oral lichen planus: A disease or a spectrum of tissue reactions? Types, causes, diagnostic algorhythms, prognosis, management strategies

“…However, an animal model has failed to definitively prove that amalgam fillings can cause oral lichenoid contact lesions . A more recent study using the same animal model (Brown Norway rats) but with different exposure modalities, suggests that nontoxic mercury can instead cause lupus‐like oral mucosal lesions …”

Oral lichen planus and related lesions. What should we accept based on the available evidence?

“…The histologic appearance of CLR does not show significant differential facts with OLP, although the presence of lymphoid follicles in the submucosa has been reported (von Blomberg‐van der Flier et al, 1987). Studies in experimental animals have failed to demonstrate conclusively that dental amalgam can generate CLR (Dunsche et al, 2003; Seno et al, 2013); likewise, in some patients with this type of lesions patch tests yield conflicting results, although it should be noted that these studies are especially productive in patients with lesions located in close contact with amalgam (Thornhill, 2003); in vitro lymphocyte proliferation tests have also failed to generate conclusive results (Nyfeler & PichIer, 1997; von Blomberg‐van der Flier et al, 1987). Definitive proof that a particular lesion is caused by contact with silver amalgam is obtained if it resolves after removal of the amalgam, which occurs most frequently in lesions in close contact with the restoration and especially in lesions located on the tongue.…”

Relação da concentração de metais pesados em amostras de água das bacias dos rios Pardo, Mogi-Guaçu, Sapucaí/Mirim e do aquífero Guarani com a etiopatogênese dos pênfigos

“…Também tem sido demonstrado que o Hg pode incitar fenômenos autoimunes em ratos e camundongos que apresentam background genético apropriado, promovendo produção de IL-4, modulação de resposta imunológica com padrão Th2 e em estudos envolvendo leões orais de lúpus induzido em camundongos foi demonstrado que o metal provoca incremento de infiltrado celular com reposta a MHC de classe II. Assim, os autores sugerem que metais, metaloides e outros elementos podem amalgamar e se ligar a moléculas celulares in vivo, produzindo alterações na sua estrutura molecular, que passam a ser reconhecidas pelo sistema imune como moléculas estranhas, assim ativando a cascata alternativa do complemento e outras moléculas inflamatórias (ABRÉU-VÉLEZ et al, 2003;SENO, 2013).…”