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Modulation by natterins of the leukocyte activation induced by the different TLR agonist

Grant number: 13/21518-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2013
Effective date (End): November 30, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Monica Valdyrce dos Anjos Lopes Ferreira
Grantee:Jéssica Giehl de Araújo
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


Immunity is the reaction to foreign substances of any type, as feedback mechanisms having components of both innate immune response(phagocyte cells , physical, biochemical barriers, natural killer cells and blood protein constituents) that have receptors that recognize conserved structures, such as leukocyte components of the adaptive immune system or specific. The Thalassophryne nattereri venom has been widely studied in different ways by our group: poisoning victims human and experimental models, biochemical and pharmacological aspects , the ability to induce neutralizing antibodies to the major toxic effects in mice and immunological mechanisms involved in this response. The majority characterization of toxins found in the venom of T. nattereri was performed by protein chemistry approach ( isolation and sequencing of internal peptides and N- terminal) and molecular (transcriptome gland venenífera fish and expression of cDNAs encoding the toxins). Using this approach we know of the existence of the fish venenífera gland of the following toxins: a family of Natterinas consisting of toxins 5, 1,2,3,4 Natterinas and P in the range of 30-45 kDa molecular mass that show homology to each other but not with proteins in the databases, and Nattectin molecular weight of 15 kDa, which shows homology to C-type lectins The Natterinas as have been named, are able to cleave the human kininogen and synthetic peptides derived from kininogen releasing Lys -BK and kallidin. The Natterinas also have an anti -inflammatory, since they are capable of inhibiting the bearing and the recruitment of neutrophils induced by LPS or chemokine KC in mice. This inhibition effect is dependent on TLR2 and TLR4 and signals derived from MyD88, leading to believe that these proteases may play a role of TLR antagonist. These results allow us to think of a possible antagonist action Natterinas in the activation of other TLR receptors. Thus, the aim of this work is to evaluate whether the Natterinas are able to antagonize other TLR receptors, by using different agonists can stimulate leukocyte rolling that will be evaluated by intravital microscopy. Investigated changes will still be possible in the signaling cascade derived from the activation of these receptors as well as the production of endogenous mediators negative.

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