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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2011.tde-26012012-093519
Document
Author
Full name
Edson Kiyotaka Ishizuka
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Silva, Carla Lima da (President)
Bortoluci, Karina Ramalho
Casa, Maisa Splendore Della
Title in Portuguese
Modulação da função de macrófagos pela nattectina: uma lectina tipo C do veneno de Thalassophryne nattereri.
Keywords in Portuguese
Citocinas
Lectinas
Macrófagos
Peixes venenosos
Toxinas em animal
Venenos de origem animal
Abstract in Portuguese
A Nattectina é uma toxina isolada do veneno de Thalassophryne nattereri que possui homologia com lectinas tipo C. Este estudo consistiu em avaliar a ação da Nattectina sobre as funções de macrófagos e a influência de citocinas Th1/Th2 nessa ativação. Nossos resultados mostram que a Nattectina induziu o aumento da expressão de moléculas coestimuladoras dependente da sinalização MAPK p38 e PI3K em macrófagos derivados da medula óssea, e também um aumento na capacidade endocítica e expressão de MHC de classe II dependentes da sinalização ERK1/2 e da ligação da Nattectina ao carboidrato. Verificamos ainda que alterações induzida pela Nattectina nos macrófagos são consistentes com a ativação clássica M1 dependente de IL-12 e IFN-g, e regulada negativamente por IL-4, IL-10 e IL-13. Por fim, verificamos uma ação coadjuvante da IL-4 com IFN-g na mobilização de SPMs (Small Peritoneal Macrophages) para cavidade peritoneal e na ativação de macrófagos. Dessa forma, a Nattectina pode ser considerada um importante agente imunomodulador capaz de modular as funções de macrófagos.
Title in English
Modulation of macrophage function by Nattectin: a C-type lectin from Thalassophryne nattereri fish venom.
Keywords in English
Cytokines
Lectins
Macrophages
Poisonous fish
Poisons of animal origin
Toxins in animal
Abstract in English
Nattectin is a toxin isolated from Thalassophryne nattereri fish venom that has homology with C-type lectin. This study was carried out to evaluate the action of Nattectin on macrophage functions and the influence of Th1/Th2 cytokines in this activation. Our results show that Nattectin induced the increased expression of costimulatory molecules dependent on MAPK p38 and PI3K signaling in bone marrow-derived macrophages, and also an increase in endocytic capacity and MHC class II expression dependent on ERK1/2 signaling and binding of Nattectin to carbohydrate. We also found that modifications induced by Nattectin in macrophages are consistent with classical (M1) activation of macrophages dependent on IL-12 and IFN-g cytokines, and negatively regulated by IL-4, IL-10 and IL-13. Finally, it was demonstrated an adjuvant role of IL-4 with IFN-g in mobilization of SPMs (Small Peritoneal Macrophages) to peritoneal cavity and also in macrophage activation. Thus, Nattectin can be considered an important immunomodulatory agent able to modulate macrophage functions.
 
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Publishing Date
2012-03-16
 
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