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J Allergy Clin Immunol ; 135(2): 477-87, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25129680

RESUMO

BACKGROUND: Contact toxicant reactions are accompanied by localized skin inflammation and concomitant increases in site-specific itch responses. The role(s) of eosinophils in these reactions is poorly understood. However, previous studies have suggested that localized eosinophil-nerve interactions at sites of inflammation significantly alter tissue innervation. OBJECTIVE: To define a potential mechanistic link between eosinophils and neurosensory responses in the skin leading to itching. METHODS: BALB/cJ mice were exposed to different contact toxicants, identifying trimellitic anhydride (TMA) for further study on the basis of inducing a robust eosinophilia accompanied by degranulation. Subsequent studies using TMA were performed with wild type versus eosinophil-deficient PHIL mice, assessing edematous responses and remodeling events such as sensory nerve innervation of the skin and induced pathophysiological responses (ie, itching). RESULTS: Exposure to TMA, but not dinitrofluorobenzene, resulted in a robust eosinophil skin infiltrate accompanied by significant levels of degranulation. Follow-up studies using TMA with wild type versus eosinophil-deficient PHIL mice showed that the induced edematous responses and histopathology were, in part, causatively linked with the presence of eosinophils. Significantly, these data also demonstrated that eosinophil-mediated events correlated with a significant increase in substance P content of the cutaneous nerves and an accompanying increase in itching, both of which were abolished in the absence of eosinophils. CONCLUSIONS: Eosinophil-mediated events following TMA contact toxicant reactions increase skin sensory nerve substance P and, in turn, increase itching responses. Thus, eosinophil-nerve interactions provide a potential mechanistic link between eosinophil-mediated events and neurosensory responses following exposure to some contact toxicants.


Assuntos
Eosinófilos/imunologia , Prurido/etiologia , Pele/imunologia , Pele/inervação , Alérgenos/administração & dosagem , Alérgenos/imunologia , Animais , Degranulação Celular , Colágeno/metabolismo , Dinitrofluorbenzeno/administração & dosagem , Dinitrofluorbenzeno/efeitos adversos , Modelos Animais de Doenças , Eosinofilia/imunologia , Eosinofilia/metabolismo , Eosinofilia/patologia , Eosinófilos/metabolismo , Fibrose , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Anidridos Ftálicos/administração & dosagem , Anidridos Ftálicos/efeitos adversos , Anidridos Ftálicos/imunologia , Prurido/diagnóstico , Pele/efeitos dos fármacos , Pele/patologia , Substância P/genética , Substância P/metabolismo
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