Publication: Inmunosenescencia prematura en ratones con una deficiencia
en la síntesis de catecolaminas. Efecto del ambiente social
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2017-02
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Elsevier
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Abstract
Introducción: La salud depende del buen funcionamiento de los sistemas homeostáticos (el nervioso, endocrino e inmunitario) y de la adecuada comunicación entre ellos. Se ha comprobado que el estado funcional y redox del sistema inmunitario es un excelente marcador de salud, y que una inmunosenescencia prematura supone una menor esperanza de vida. Dado que las catecolaminas modulan la funcionalidad de las células inmunitarias, la alteración en su síntesis podría contribuir a esa inmunosenescencia. Entre las estrategias que se pueden utilizar para controlarla está el ambiente social.
Objetivo: Comprobar si una haploinsuficiencia de la tirosina hidroxilasa (TH), enzima limitante de la síntesis de catecolaminas, generaría una inmunosenescencia prematura, y si es posible la modulación de esta por el ambiente social.
Material y métodos: Se usaron ratones machos ICR-CD1 adultos (9 ± 1 meses) hemizigotos (HZ) para la tirosina hidroxilasa (TH-HZ) y controles (WT), que fueron distribuidos en cuatro subgrupos: WT > 50% (en la jaula, la proporción de WT fue mayor al 50%), WT < 50%, TH-HZ < 50% y TH-HZ > 50%. En leucocitos peritoneales se valoró la fagocitosis, quimiotaxis y linfoproliferación en presencia de lipopolisacárido. También, la actividad de las enzimas antioxidantes glutatión reductasa y glutatión peroxidasa, y el cociente glutatión oxidado/glutatión reducido. Resultados: Los TH-HZ > 50% presentaron, en leucocitos, una funcionalidad y estado redox deteriorados respecto a WT > 50 y similar a ratones viejos. Sin embargo, los TH-HZ < 50% mostraron valores similares a los WT < 50%.
Conclusión: Una haploinsuficiencia de la enzima TH provoca una inmunosenescencia prematura, la cual puede ser compensada por la convivencia con un número apropiado de animales WT.
Introduction: Healthy state depends on the appropriate function of the homeostatic systems (nervous, endocrine and immune systems) and the correct communication between them. The functional and redox state of the immune system is an excellent marker of health, and animals with premature immunosenescence show a shorter lifespan. Since catecholamines modulate the function of immune cells, the alteration in their synthesis could provoke immunosenescence. The social environment could be a strategy for modulating this immunosenescence. Aim: To determine if an haploinsufficiency oftyrosine hydroxylase (TH),the limiting enzyme of synthesis of catecholamines, may produce a premature immunosenescence and if this immunosenescence could be modulated by the social environment. Materials and methods: Adult (9 ± 1 months) male ICR-CD1 mice with deletion of a single allele (hemizygotic: HZ) of the tyrosine hydroxylase enzyme (TH-HZ) and wild-type (WT) mice were used. Animals were housed in four subgroups: WT > 50% (in the cage, the proportion of WT mice was higher than 50% in relation to TH-HZ), WT < 50%, TH-HZ < 50% and TH-HZ > 50%. Peritoneal leukocytes were collected and phagocytosis, chemotaxis and proliferation of lymphocytes in the presence of lipopolysaccharide were analyzed. Glutathione reductase and glutathione peroxidase activities as well as oxidized/reduced glutathione ratio were studied. Results: TH-HZ > 50% mice showed a deteriorated function and redox state in leukocytes respect to WT > 50% and similar to old mice. However, TH-HZ < 50% animals had similar values to those found in WT < 50% mice. Conclusion: The haploinsufficiency of TH generates premature immunosenescence, which appears to be compensated by living together with an appropriate number of WT animals.
Introduction: Healthy state depends on the appropriate function of the homeostatic systems (nervous, endocrine and immune systems) and the correct communication between them. The functional and redox state of the immune system is an excellent marker of health, and animals with premature immunosenescence show a shorter lifespan. Since catecholamines modulate the function of immune cells, the alteration in their synthesis could provoke immunosenescence. The social environment could be a strategy for modulating this immunosenescence. Aim: To determine if an haploinsufficiency oftyrosine hydroxylase (TH),the limiting enzyme of synthesis of catecholamines, may produce a premature immunosenescence and if this immunosenescence could be modulated by the social environment. Materials and methods: Adult (9 ± 1 months) male ICR-CD1 mice with deletion of a single allele (hemizygotic: HZ) of the tyrosine hydroxylase enzyme (TH-HZ) and wild-type (WT) mice were used. Animals were housed in four subgroups: WT > 50% (in the cage, the proportion of WT mice was higher than 50% in relation to TH-HZ), WT < 50%, TH-HZ < 50% and TH-HZ > 50%. Peritoneal leukocytes were collected and phagocytosis, chemotaxis and proliferation of lymphocytes in the presence of lipopolysaccharide were analyzed. Glutathione reductase and glutathione peroxidase activities as well as oxidized/reduced glutathione ratio were studied. Results: TH-HZ > 50% mice showed a deteriorated function and redox state in leukocytes respect to WT > 50% and similar to old mice. However, TH-HZ < 50% animals had similar values to those found in WT < 50% mice. Conclusion: The haploinsufficiency of TH generates premature immunosenescence, which appears to be compensated by living together with an appropriate number of WT animals.