Publication: Papel homeostático e inflamatorio de neutrófilos senescentes
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2018-09-20
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Universidad Complutense de Madrid
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Abstract
Los neutrófilos son los leucocitos más abundantes en la circulación humana y representan la primera barrera de defensa contra microorganismos patógenos. Su número en circulación muestra un comportamiento temporalmente oscilatorio, con una periodicidad circadiana. Son células con una vida corta, en el rango de horas desde que salen de la médula ósea hasta que son eliminadas de la circulación (clearance). En ese lapso de tiempo sufren un proceso conocido como envejecimiento que provoca cambios fenotípicos en varios marcadores de superficie y precede en el tiempo a la fase de clearance. Así, durante el día los neutrófilos muestran un fenotipo esencialmente “envejecido” (también llamado senescente) y durante la noche un fenotipo “fresco”. En este trabajo hemos analizado este proceso de envejecimiento de los neutrófilos en ratones y demostramos que está controlado por el reloj molecular y la señalización de dos receptores de quimioquinas, CXCR2 y CXCR4, que funcionan de manera antagónica. Hemos analizado el proceso transcriptómicamente y demostramos que se trata de un programa transcripcional global que afecta a gran cantidad de rutas bioquímicas y dota de propiedades específicas a los neutrófilos. Para estudiar éstas en detalle hemos generado y caracterizado ratones mutantes específicamente en neutrófilos para los genes que regulan el envejecimiento...
Neutrophils are the most abundant leukocytes in human circulation, and the first line of defense against pathogens. Their numbers follow a circadian pattern of oscillation in blood. They are short-lived, with lifetimes in the range of hours from the time they leave the bone marrow to the moment they are removed from blood (clearance). In the time they spend in the circulation neutrophils undergo a process of “aging” that promotes phenotypic changes on several surface markers and precedes the clearance phase: during the day neutrophils show an “aged” (also called senescent) phenotype and during the night a “fresh” phenotype. In this work we have analyzed this process of neutrophil aging in mice and we show that it is controlled by both the molecular clock and antagonistic signaling of two chemokine receptors: CXCR2 and CXCR4. We performed mass RNA sequencing, and found that this process is a global transcriptional program that affects several biochemical pathways and endows neutrophils with specific properties. To study these properties in detail we generated and characterized mice with neutrophil-specific deficiencies in genes that control the process of aging...
Neutrophils are the most abundant leukocytes in human circulation, and the first line of defense against pathogens. Their numbers follow a circadian pattern of oscillation in blood. They are short-lived, with lifetimes in the range of hours from the time they leave the bone marrow to the moment they are removed from blood (clearance). In the time they spend in the circulation neutrophils undergo a process of “aging” that promotes phenotypic changes on several surface markers and precedes the clearance phase: during the day neutrophils show an “aged” (also called senescent) phenotype and during the night a “fresh” phenotype. In this work we have analyzed this process of neutrophil aging in mice and we show that it is controlled by both the molecular clock and antagonistic signaling of two chemokine receptors: CXCR2 and CXCR4. We performed mass RNA sequencing, and found that this process is a global transcriptional program that affects several biochemical pathways and endows neutrophils with specific properties. To study these properties in detail we generated and characterized mice with neutrophil-specific deficiencies in genes that control the process of aging...
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Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Bioquímica y Biología Molecular I, leída el 10 de Julio de 2017