Efeito dos quelantes de ferro deferoxamina (DFO) e mimosina na função de neutrófilos humanos.
Data
2021-08-05
Autores
Santos, Nubia Gonçalves dos 
Orientadores
Simon, Karin Argenti
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Os leucócitos polimorfonucleares possuem uma maquinaria complexa e diferenciada para lidar com infecções recorrentes em nosso corpo. A produção de espécies reativas de oxigênio (ERO) e nitrogênio (ERN) são fundamentais para o desempenho deste tipo celular, pois desencadeiam a formação de outros mecanismos efetores e são eficazes na degradação de microorganismos em fagolisossomas. O descontrole dessas funções pode acarretar, entre outros problemas, em estresse oxidativo, e consequentemente, trazer riscos à saúde humana. O estudo propôs testar e discutir possíveis moduladores da classe de quelantes em processos inflamatórios. Para isso, avaliou-se parâmetros de funcionalidade in vitro de leucócitos polimorfonucleares humanos, isolados de sangue periférico, na presença dos agentes quelantes de ferro deferoxamina (DFO) e do aminoácido não protéico mimosina. Com base nos conhecimentos sobre a produção intencional de ERO e de ERN, o “burst” oxidativo, aplicou-se o método de luminescência amplificada por luminol, estabelecendo um gradiente de concentração. O tratamento com os quelantes apontou uma diminuição significativa na produção de espécies reativas em células estimuladas com PMA e Zymosan. Os diferentes estímulos também influenciaram na intensidade com que essa diminuição ocorreu. Ainda não é possível descrever completamente o mecanismo chave por trás dessas reações, contudo os resultados obtidos corroboram a relevância do ferro na produção de ERO por neutrófilos estimulados e indicam um papel para o uso de quelantes na modulação da função oxidativa dessas células.
Polymorphonuclear leukocytes have a complex and distinctive mechanism to deal with recurrent infections in our body. The production of Reactive Oxygen (ROS) and Nitrogen (RNS) Species is fundamental for performance of this cell type, as they trigger the formation of other effector mechanisms and are effective in the degradation of microorganisms in phagolysosomes. The lack of control of these functions can cause, among other problems, oxidative stress and consequently, pose risks to human health. This study tested and discussed possible modulators of a class of chelators in inflammatory processes. For this purpose, this study evaluated in vitro functionality parameters of human polymorphonuclear leukocytes isolated from peripheral blood in the presence of the iron chelating agents deferoxamine (DFO) and the nonprotein amino acid mimosine. Based on the knowledge about the deliberate production of ROS and RNS, the oxidative burst, the method of luminol-amplified chemiluminescence was applied, establishing a concentration gradient. Treatment with chelators showed a significant decrease in the production of reactive species in cells stimulated with PMA and Zymosan. Different stimuli also affected the intensity of the decreased response. It is not yet possible to completely describe the key mechanism for these reactions, however our results corroborate the importance of iron in the production of ROS by stimulated neutrophils and indicate a role for the use of chelators in modulating the oxidative function of these cells.
Polymorphonuclear leukocytes have a complex and distinctive mechanism to deal with recurrent infections in our body. The production of Reactive Oxygen (ROS) and Nitrogen (RNS) Species is fundamental for performance of this cell type, as they trigger the formation of other effector mechanisms and are effective in the degradation of microorganisms in phagolysosomes. The lack of control of these functions can cause, among other problems, oxidative stress and consequently, pose risks to human health. This study tested and discussed possible modulators of a class of chelators in inflammatory processes. For this purpose, this study evaluated in vitro functionality parameters of human polymorphonuclear leukocytes isolated from peripheral blood in the presence of the iron chelating agents deferoxamine (DFO) and the nonprotein amino acid mimosine. Based on the knowledge about the deliberate production of ROS and RNS, the oxidative burst, the method of luminol-amplified chemiluminescence was applied, establishing a concentration gradient. Treatment with chelators showed a significant decrease in the production of reactive species in cells stimulated with PMA and Zymosan. Different stimuli also affected the intensity of the decreased response. It is not yet possible to completely describe the key mechanism for these reactions, however our results corroborate the importance of iron in the production of ROS by stimulated neutrophils and indicate a role for the use of chelators in modulating the oxidative function of these cells.