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Action of the immunomodulator P-MAPA on the complement system and Toll like receptors in a model of inflammation induced by lipopolysaccharide.

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Author(s):
Mariana Torrente Gonçalves
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Denise Vilarinho Tambourgi; Ângela Silva Barbosa; Enéas de Carvalho
Advisor: Denise Vilarinho Tambourgi
Abstract

P-MAPA, a protein aggregate has been described as a promising immunomodulator, however, its role on the complement system and Toll-like receptors (TLRs) is unknown. In the study, P-MAPA has promoted activation of the complement\'s classical and alternative pathways and the production of C3a and C5a. Using an ex vivo model of human whole blood, the compound promoted increase of CD11b and CD14 expression, decrease of C5aR, TLR2 and TLR4, in peripheral blood leucocytes and when combined with LPS, but did not change C3aR expression. P-MAPA promoted reduction of IFN-g in plasma, increased production of TNF-α, IL-8, IL-12 and peroxynitrite, but did not induce the production of superoxide, IL-6, IL-1β, TGF-β or IL-10. Through in vivo tests, we were able to determine a lethal dose for P-MAPA. Altogether, our data indicate that P-MAPA has proinflammatory action in ex vivo model of human whole blood and that the treatment combined with LPS leads to amplification of its effects. (AU)

FAPESP's process: 12/05306-8 - Action of the immunomodulator P-MAPA on the complement system and Toll like receptors in a model of inflammation induced by LPS
Grantee:Mariana Torrente Gonçalves
Support Opportunities: Scholarships in Brazil - Master