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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2019.tde-14042022-100915
Document
Author
Full name
Tamíris Isabela Guidugli
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Ribeiro Filho, Orlando Garcia (President)
Bassères, Daniela Sanchez
Isaac, Lourdes
Katz, Iana Suly Santos
Title in Portuguese
O estudo das células mieloderivadas supressoras na tumorigênese pulmonar em camundongos selecionados para máxima ou mínima resposta inflamatória aguda
Keywords in Portuguese
Acute inflammation
MDSC
Pulmonary tumorigenesis
Abstract in Portuguese
Estudos sugerem que as células mieloderivadas supressoras (MDSCs) desempenham um papel crítico durante a progressão do câncer. Os tumores alteram a hematopoiese normal e conduzem ao acúmulo de MDSC no local do tumor. Estas células exercem uma ação supressora do sistema imune. Considerando-se que os camundongos fenotipicamente selecionados para máxima (AIRmax) ou mínima (AIRmin) resposta inflamatória aguda apresentam diferenças na produção de células na medula óssea e, também, apresentam uma diferença no desenvolvimento do tumor induzido por Uretana, comparamos a população celular MDSC em camundongos AIR. Estes camundongos foram tratados com duas injeções ip de Uretana com um intervalo de 48h para indução da tumorigênese e foram observados durante 60 dias após o tratamento. As análises histológicas mostraram que 20 dias após a injeção com Uretana, os pulmões dos AIRmin apresentaram um processo inflamatório crônico, caracterizando o início de uma possível lesão, enquanto que nos animais AIRmax, independente do período após o tratamento, apresentaram apenas um pequeno infiltrado de neutrófilos. Estes resultados corroboram com os resultados obtidos nas análises morfológicas, em que os animais AIRmax apresentaram mais neutrófilos maduros, enquanto que os AIRmin apresentam neutrófilos imaturos. Os resultados da citometria de fluxo mostraram que os AIRmax possuem um número maior de células mielóides maduras, caracterizadas como CD11b&#43/Gr1&#43/CD38- e Linfócitos TCD8, enquanto os AIRmin apresentam altos níveis de células mielóides imaturas, CD11b&#43/Gr1&#43CD38&#43 e Linfócitos T reguladores. Os ensaios de co-cultura mostraram que estas células mielóides imaturas presentes nos AIRmin apresentam uma função supressora sobre os Linfócitos T, e por isso, podem ser caracterizadas como MDSCs, contribuindo para a sensibilidade à tumorigênese.
Title in English
The study of myeloderivated suppressor cells on lung tumorgenesis in mice genetically selected for maximum or minimum acute inflammatory reactivity
Keywords in English
Acute inflammation
MDSC
Pulmonary tumorigenesis
Abstract in English
Studies suggest that myeloderivated suppressor cells (MDSCs) play a critical role during the progression of cancer. Tumors cells alter the normal hematopoiesis and leads MDSC accumulation at the tumor site. These cells exert a suppressive function on the immune system. Considering that mice phenotypically selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory reaction present difference in the myeloid cell production and exhibit a difference in development of chemically induced tumor, we compared the MDSC cells population in AIR mices. Mice were treated with two ip injections of Urethane at 48-h interval for lung tumor induction and were observed for 60 days after treatment. Histological analysis showed that 20 days after Urethane injection, AIRmin's lungs presented a chronic inflammatory process, characterizing the onset of a possible lesion, whereas in AIRmax, regardless of the period after treatment, they presented only a small infiltrate of neutrophils. These results corroborate the results obtained in the morphological analysis, which AIRmaxs lungs presented more mature neutrophils, while AIRmin presented immature neutrophils. The flow cytometry results showed that AIRmax mice had a higher number of mature cells, characterized as CD11b&#43/Gr1&#43/CD38-, and CD8 T lymphocytes, while AIRmin mice showed higher immature cells, CD11b&#43/Gr1&#43/CD38&#43, and regulatory T lymphocytes. Co-culture assays showed that the immature myeloid cells derived from AIRmin mice have a suppressive function on T lymphocytes, and therefore can be characterized as MDSCs, which contribute to lung tumorigenesis susceptible.
 
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Publishing Date
2022-05-19
 
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