Título :	Papel das etapas precoces de ativação da produção de EROs na indução das NETs
Autor :	Damascena, Hylane Luiz
Orientador(es)::	Fontes, Wagner
Assunto::	Armadilhas extracelulares (NETs) Neutrófilos Polimorfonucleares
Fecha de publicación :	1-abr-2022
Data de defesa::	8-dic-2021
Citación :	DAMASCENA, Hylane Luiz. Papel das etapas precoces de ativação da produção de EROs na indução das NETs. 2021. 121 f., il. Tese (Doutorado em Patologia Molecular) — Universidade de Brasília, Brasília, 2021.
Abstract:	Neutrophils are the most abundant innate immune cell in the peripheral blood. They are the first to arrive at the infection site and among their defense mechanisms, they use extracellular traps (NETs) that promote extracellular capture and death of microorganisms and occur independently of phagocytosis and intracellular death. Despite being a beneficial mechanism for the immune defense of the host, NETs have been associated with several diseases, due to the release of DNA and proteins that favor the formation of thrombi, as well as being recognized as autoantigens. In this way, the regulated performance of NETs is important for the defense of the host, while an intense deregulated response leads to damage. One of the known pathways of NETs is suicidal NETosis. This formation of NETs is dependent on ROS produced by NADPH oxidase, which triggers several cellular mechanisms leading to the release of nuclear DNA. In order to elucidate the involvement of proteins and pathways during the initial period of NETosis (60 minutes) associated to the respiratory burst, we analyzed the proteomic changes of neutrophils induced by PMA and controlled by apocinin, to produce NETs. Kinetic analysis of ROS production showed that the NADPH oxidase inhibition after the PMA stimulus has less influence on ROS generation, compared to inhibition before stimulus. The production of ROS observed in the first 20min was enough to trigger the formation of NETs, favoring microorganisms’ death by entrapment. Furthermore, ROS production in the first minutes is able to initiate proteomic changes associated to NETs formation. Proteins related to actin polymerization (LIMS1, ADAM10 and AMBP) were associated to cellular migration. Curiously, late cellular migration (after 20min.), that was not associated to NETs formation, seems not associated to actin polymerization, however, associated to tubulin and vitronectin. Moreover, this study showed the first time that neutrophils can release the C4 component of the complement system, suggesting the probable activation of complement pathway contributes to NETs extrusion.
metadata.dc.description.unidade:	Faculdade de Medicina (FM)
Descripción :	Tese (doutorado) — Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Patologia Molecular, 2021.
metadata.dc.description.ppg:	Programa de Pós-Graduação em Patologia Molecular
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