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Toxicology ; 226(2-3): 197-207, 2006 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-16920245

RESUMO

2,3,7,8-Tetrachloro-dibenzo-p-dioxin (TCDD) is an ubiquitously distributed xenobiotic. It has been postulated that the effects of TCDD on T-lymphocytes are mediated by modulation of the thymic microenvironment. There is growing evidence of a modified interplay between thymocytes and thymic epithelium related to changes in extracellular matrix (ECM) proteins. Eighteen male marmosets (Callithrix jacchus) were treated with single subcutaneous TCDD doses (1, 10, 100 ng/kg body weight) or vehicle and sacrificed 2 or 4 weeks thereafter. Thymus samples were stained with fluorescein isothiocyanate-conjugated antibodies for ECM proteins and examined immunohistochemically by semi-quantitative image analysis. Thymus samples of animals treated with 1 and 10 ng/kg were additionally analysed by Western blotting for ECM proteins, transforming growth factor-beta(1) (TGF-beta(1)) and integrin chain content (CD49a, CD49e, CD49f and CD29). Monkeys showed no overt signs of toxicity after TCDD treatment. Immunohistochemistry revealed an increase of ECM proteins at 100 ng/kg after 2 and 4 weeks. Western blotting confirmed immunohistochemistry showing a dose-dependent increase of several ECM proteins in animals treated with the lower TCDD doses of 1 and 10 ng/kg. Additionally, dose-dependent increases were observed in integrin chain and TGF-beta(1) contents. We demonstrated changes of thymic ECM in marmosets following low single TCDD doses. Combined with altered integrin expression and enhanced TGF-beta(1) stimulation our findings suggest a modified interplay between thymic epithelium and thymocytes. The extracellular matrix may play a more central role in mediating adverse effects of TCDD in organs than yet acknowledged.


Assuntos
Poluentes Ambientais/toxicidade , Proteínas da Matriz Extracelular/metabolismo , Matriz Extracelular/metabolismo , Dibenzodioxinas Policloradas/toxicidade , Timo/efeitos dos fármacos , Animais , Western Blotting , Callithrix , Colágeno/metabolismo , Densitometria , Matriz Extracelular/efeitos dos fármacos , Fibronectinas/metabolismo , Imunofluorescência , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Integrinas/metabolismo , Laminina/metabolismo , Masculino , Receptores de Fatores de Crescimento Transformadores beta/efeitos dos fármacos , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Timo/patologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1
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