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Doctoral Thesis
DOI
10.11606/T.42.2011.tde-20032012-155547
Document
Author
Full name
Alexandra dos Anjos Cassado
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Bortoluci, Karina Ramalho (President)
Barbuto, Jose Alexandre Marzagao
Gazzinelli, Ricardo Tostes
Keller, Alexandre de Castro
Silva, Carla Lima da
Title in Portuguese
Heterogeneidade dos macrófagos peritoneais.
Keywords in Portuguese
Cavidade peritoneal
Heterogeneidade
Imunidade ativa
Macrófagos
Monócitos
Peritônio
Abstract in Portuguese
Os macrófagos (MΦs) compõem uma população celular altamente heterogênea, e são extensivamente adotados como ferramenta experimental, em especial os MΦs peritoneais murinos. O objetivo desse trabalho foi revisitar o peritônio dando ênfase à heterogeneidade dos MΦs. Duas populações distintas compõem os MΦ peritoneais residentes: LPM (Large Peritoneal Macrophage) e SPM (Small Peritoneal Macrophage). Todas as condições proporcionadas in vivo resultam no desaparecimento de LPM, aumento de SPM e influxo de monócitos. Em paralelo, ocorre uma diminuição na marcação para b-galactosidase (marcador de senescência) e um aumento na produção de Óxido Nítrico (NO) e na frequência de células F4/80+IL-12+ após a subseqüente estimulação com LPS e IFN-g, que parece ser às custas da SPM. Além disso, parece haver uma especialização onde LPM assume um perfil M2 após inoculação de zimosan, e SPM um perfil M1 após reestimulo com LPS ou IFN-g.Esses dados sugerem que renovação celular que ocorre no peritônio após estimulação, parece ser benéfica para a resposta celular frente a estímulos infecciosos.
Title in English
Peritoneal macrophage heterogeneity.
Keywords in English
Active immunity
Heterogeneity
Macrophages
Monocytes
Peritoneal cavity
Peritoneum
Abstract in English
Macrophages (MΦ) are a heterogeneous population extensively adopted as experimental model, especially peritoneal MΦ. Then, the aim of this work was to revisit peritoneal cavity looking for MΦ heterogeneity. Peritoneal MΦ comprise two distinct subpopulations: LPM (Large Peritoneal Macrophage) and SPM (Small Peritoneal Macrophage). The different conditions proporcioned in vivo, resulted in the disappearance of LPM and the accumulation of SPM and monocytes. In parallel, adherent cells isolated from stimulated mice displayed reduced staining for b-galactosidase (senescence marker). Further, an increase in nitric oxide (NO) production and IL-12-producing cells frequency was observed in response to LPS/FN-g re-stimulation. In addition, there was a specialization of activation profile marked by a M2 activation profile after zymosan administered in vivo assumed by LPM, and SPM showed a bias to M1 after re-stimulation with LPS/IFN-g. Then, the substitution of LPM by a robust SPM and monocytes in response to infectious stimuli greatly improves peritoneal effector activity.
 
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Publishing Date
2012-05-25
 
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