O papel da heme oxigenase-1 na leishmaniose visceral canina
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Data
2016-08-19
Autores
Almeida, Breno Fernando Martins de [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A leishmaniose visceral canina (LVC) é uma doença crônica que causa imunossupressão nos animais doentes, principalmente por prejudicar a resposta imunológica celular, diminuindo a proliferação linfocitária e a capacidade fagocítica das células de defesa. Recentemente, a enzima heme oxigenase-1 (HO-1) vem ganhando destaque por estar envolvida na regulação da resposta imune celular em algumas condições patológicas, sendo uma enzima induzível por condições de estresse, como o estresse oxidativo que sabidamente ocorre na LVC. Nesse contexto, esse trabalho teve por objetivo determinar o papel da HO-1 na LVC, determinando sua concentração e expressão em cães infectados e saudáveis, correlacionando-a com o estresse oxidativo, carga parasitária e IL-10. Objetivou-se também avaliar o efeito da indução e inibição da enzima sobre a resposta linfoproliferativa de células de linfonodo de cães doentes e sobre a taxa de infecção macrofágica por promastigotas de Leishmania infantum, determinando as citocinas envolvidas. Os cães com LVC apresentaram marcante estresse oxidativo e aumento da concentração e expressão de HO-1, obtendo-se correlação positiva entre HO-1e estresse oxidativo e IL-10 de acordo com o tecido analisado. A inibição de HO-1 aumentou a taxa de proliferação celular na presença de antígeno solúvel de L. infantum, enquanto a indução de HO-1 diminuiu a taxa de proliferação antígeno-específica e aumentou a taxa de infecção macrofágica e o número de amastigotas por macrófago. Conclui-se que o aumento do metabolismo da HO-1 observado na LVC está associado ao estresse oxidativo presente nesses cães e pode ser um dos mecanismos envolvidos na inibição da resposta linfoproliferativa e perpetuação da infecção, com inibição da atividade microbicida macrofágica.
Canine visceral leishmaniasis (CVL) is a chronic disease that causes immunosuppression by reducing the cellular response of infected animals, impairing the cell proliferation and the phagocytic ability of defense cells. Recently, heme oxygenase-1 (HO-1) has been highlighted for being involved in regulation of cell response in certain pathological conditions, and for being an enzyme that can be induced by stress conditions, such as oxidative stress, that is known to occur in CVL. In this context, this study aimed to determine the role of HO-1 in CVL, determining its levels and expression in infected and healthy dogs, correlating these findings with oxidative stress, parasite load and IL-10. The effect of induction and inhibition of HO-1 on lymphoproliferative response by lymph node cells of infected dogs and macrophage infection rate by promastigotes of Leishmania infantum were also evaluated. Dogs with CVL showed marked oxidative stress and increased levels and expression of HO-1, obtaining a positive correlation between HO-1 and oxidative stress and IL-10 in a tissue-dependent way. Inhibition of HO-1 increased proliferation rate in the presence of L. infantum soluble antigen, while induction of HO-1 decreased antigen-specific proliferation and increased macrophage infection rate and number of amastigotes per macrophage. The increase in HO-1 metabolism observed in CVL is associated to oxidative stress present in these dogs and could be one of the mechanisms involved in the inhibition of the lymphoproliferative response, permitting the perpetuation of infection by the inhibition of macrophage microbicidal activity.
Canine visceral leishmaniasis (CVL) is a chronic disease that causes immunosuppression by reducing the cellular response of infected animals, impairing the cell proliferation and the phagocytic ability of defense cells. Recently, heme oxygenase-1 (HO-1) has been highlighted for being involved in regulation of cell response in certain pathological conditions, and for being an enzyme that can be induced by stress conditions, such as oxidative stress, that is known to occur in CVL. In this context, this study aimed to determine the role of HO-1 in CVL, determining its levels and expression in infected and healthy dogs, correlating these findings with oxidative stress, parasite load and IL-10. The effect of induction and inhibition of HO-1 on lymphoproliferative response by lymph node cells of infected dogs and macrophage infection rate by promastigotes of Leishmania infantum were also evaluated. Dogs with CVL showed marked oxidative stress and increased levels and expression of HO-1, obtaining a positive correlation between HO-1 and oxidative stress and IL-10 in a tissue-dependent way. Inhibition of HO-1 increased proliferation rate in the presence of L. infantum soluble antigen, while induction of HO-1 decreased antigen-specific proliferation and increased macrophage infection rate and number of amastigotes per macrophage. The increase in HO-1 metabolism observed in CVL is associated to oxidative stress present in these dogs and could be one of the mechanisms involved in the inhibition of the lymphoproliferative response, permitting the perpetuation of infection by the inhibition of macrophage microbicidal activity.
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Palavras-chave
Cão, HSP32, Leishmania infantum, Dog