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Doctoral Thesis
DOI
10.11606/T.42.2012.tde-30012013-094319
Document
Author
Full name
Márcio José Ferreira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Ferreira, Mônica Valdyrce dos Anjos Lopes (President)
Câmara, Niels Olsen Saraiva
Scavone, Cristoforo
Soriano, Francisco Garcia
Vessoni, Sandra Coccuzzo Sampaio
Title in Portuguese
O papel crítico da sinalização TLR/MyD88 no efeito inibitório das proteases Natterinas no recrutamento celular.
Keywords in Portuguese
Inflamação
Peixes venenosos
Receptores imunológicos
Sistema imune
Veneno de origem animal
Abstract in Portuguese
Neste trabalho avaliamos se as Natterinas (NTR), proteínas majoritárias presentes no veneno do peixe peçonhento T. nattereri, são as responsáveis pela a ação inibitória do recrutamento de leucócitos durante a inflamação e os mecanismos moleculares envolvidos neste processo. Utilizando análises de microscopia intravital tratamos os animais com as NTR e 6 h depois induzimos o rolamento de leucócitos com KC, LPS ou agonista de PAR-4 sobre a microcirculação. Os dados mostraram que o tratamento com as NTR inibem o rolamento e a migração de leucócitos induzido pela KC e pelo LPS. Além disso, o efeito inibitório das NTR depende parcialmente da sua atividade proteásica e não está relacionado com a clivagem proteolítica da quimiocina KC ou com a indução de reguladores endógenos como IL-10, corticóides, a enzima HO-1 ou IL-1Ra. O efeito inibitório parece ser dependente da ativação da sinalização TLR/MyD88 e PI3K e das proteínas serina/treonina fosfatases, contribuindo de forma significativa na sobrevida de animais induzidos a endotoxemia por LPS.
Title in English
The critical role of TLR/MyD88 signaling in the inhibitory effect of proteases Natterins in cell recruitment.
Keywords in English
Immune receptors
Immune system
Inflammation
Poison animal
Poisonous fish
Abstract in English
In this work we evaluated whether Natterins (NTR) the majority proteins present in the venom of Thalassophryne nattereri venomous fish are responsible for the inhibitory action of leukocyte recruitment during inflammation and the molecular mechanisms involved in this process. Using intravital microscopy analysis we treated the animals with NTR and 6 h after we induced the leukocyte rolling by topical of KC, LPS or agonist of PAR-4 on the microcirculation. The data showed that treatment with NTR inhibited the leukocyte rolling and migration induced by LPS and KC. Moreover, the inhibitory effect of NTR depends partly on its proteinase activity and is not related to the proteolytic cleavage of the chemokine or KC nor with the induction of endogenous regulators such as IL-10, corticoids, the HO-1 or IL-1Ra. The inhibitory effect is dependent on the activation of PI3K and TLR/MyD88 signaling and protein serine/threonine phosphatases, contributing significantly to the survival of animals endotoxemia induced by LPS.
 
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MarcioJoseFerreira_P.pdf (627.90 Kbytes)
Publishing Date
2013-03-21
 
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