• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2020.tde-16122019-170931
Document
Author
Full name
Ester Wilma Pacheco Gonzales
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Mendes, Joao Gustavo Pessini Amarante (President)
Cassado, Alexandra dos Anjos
Salles, Érika Machado de
Vasconcelos, José Ronnie Carvalho de
Title in Portuguese
Avaliação de macrófagos peritoneais em camundongos C57BI/6 bim+/+ e bim-/-
Keywords in Portuguese
BIM
Large Peritoneal Macrophages
Small Peritoneal Macrophages
Abstract in Portuguese
Macrófagos são células do sistema imunológico que atuam de maneira importante no sistema imune inato, por meio de fagocitose e secreção de citocinas, bem como na estimulação do sistema imune adaptativo, via apresentação de antígenos no contexto de moléculas do MHC e secreção de citocinas. É importante destacar que além de atuar na defesa contra microrganismos patogênicos, os macrófagos também atuam na eliminação de células cancerosas e de células apoptóticas. Macrófagos residentes teciduais possuem diferentes características de acordo com seu ambiente tecidual. No peritônio, em especial maneira, há duas subpopulações distintas, Large Peritoneal Macrophage (LPM) e Small Peritoneal Macrophages (SPM) que possuem características fenotípicas e funcionais distintas. Sendo que LPM predomina no peritônio em condições basais e SPM predomina em condições inflamatórias. A via intrínseca da apoptose é controlada pela família de proteínas Bcl-2, que possui membros anti-apoptóticos e pró-apoptóticos. Dentre os membros desta família, a proteína pró-apoptótica Bim tem grande destaque, visto que tem sido associada ao controle da resposta imune adaptativa, controlando a contração dos linfócitos ao término de uma resposta imune, eliminação de células B e T auto-reativas, entre outros achados. Apesar de sua grande importância, pouco há descrito na literatura de seu papel em macrófagos. Também permanece obscuro, o efeito da ausência de Bim na diferenciação e ativação de macrófagos. Recentemente, nosso grupo de pesquisa observou que macrófagos bim-/- são mais resistentes ao efeito citopático da infecção pelo T. cruzi, o que sugere que a deficiência de bim pode influenciar a resposta dos macrófagos frente a diferentes infecções. Neste contexto, investigamos neste trabalho o papel de bim sobre macrófagos LPM e SPM sob condições basais e inflamatórias. Para tanto usamos como modelo animal camundongos C57Bl/6 bim+/+ e bim-/- machos e fêmeas. Foi realizada caracterização fenotípica das populações peritoneais por imunofenotipagem e nossos resultados demonstraram que ausência de bim afeta o compartimento de células F4/80+ no peritônio de machos e fêmeas em estado basal. Além disso, em condições basais, ausência de bim leva ao aumento de ativação por células LPM e SPM dependente de gênero. Por último, avaliamos a sensibilidade de macrófagos peritoneais deficientes de bim frente a drogas apoptóticas com actinomicina D e estaurosporina in vitro. Macrófagos bim-/- não apresentaram maior resistência que macrófagos bim+/+.
Title in English
Avaliation of peritoneal macrophages in bim+/+ e bim-/- mice
Keywords in English
BIM
Large Peritoneal Macrophages
Small Peritoneal Macrophages
Abstract in English
Macrophages are cells of the immune system that play an important role in the innate immune system, through phagocytosis and secretion of cytokines, as well as in the stimulation of the adaptive immune system, through the presentation of antigens in the context of MHC molecules and secretion of cytokines. It is important to highlight that besides acting in defense against pathogenic microorganisms, macrophages also act in the elimination of cancerous cells and apoptotic cells. Tissue resident macrophages have different characteristics according to their tissue environment. In the peritoneum, in particular, there are two distinct subpopulations, Large Peritoneal Macrophage (LPM) and Small Peritoneal Macrophages (SPM) that have distinct phenotypic and functional characteristics. LPM predominates in the peritoneum under basal conditions and SPM predominates in inflammatory conditions. The intrinsic pathway of apoptosis is controlled by the Bcl-2 family of proteins, which has anti-apoptotic and pro-apoptotic members. Among the members of this family, the pro-apoptotic protein Bim has a great prominence, because it has been associated with the control of the adaptive immune response, controlling the contraction of the lymphocytes at the end of an immune response, elimination of self-reactive B and T cells, among other findings. Despite its great importance, little has been described in the literature about its role in macrophages. Also remains unclear, the effect of the absence of Bim on the differentiation and activation of macrophages. Recently, our research group has found that bim-/- macrophages are more resistant to the cytopathic effect of T. cruzi infection, suggesting that bim deficiency may influence the response of macrophages to different infections. In this context, in this work we investigated the role of bim on LPM and SPM macrophages under basal and inflammatory conditions. Thus, we used as animal model C57Bl/6 bim+/+ and bim-/- males and females. Phenotypic characterization of the peritoneal populations was performed by immunophenotyping and our results demonstrated that the absence of bim affects the F4/80+ cell compartment in the peritoneum of males and females in the steady state. In addition, in basal conditions the lack of bim leads to increased activation by LPM and SPM cells in gender-dependent manner. Finally, we evaluated the sensitivity of bim-deficient peritoneal macrophages to apoptotic drugs such as actinomycin D and staurosporine in vitro. Bim-/- macrophages showed no greater resistance than bim+/+ macrophages.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2020-01-08
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2021. All rights reserved.