Study of the effect of hypoxia on activation, degranulation and oxidative profile of neutrophils in patients with alpha-1 antitrypsin deficiency
[EN] The number of neutrophils in the lungs of patients with alpha 1 antitrypsin deficiency (AATD) is significantly higher than in those of healthy individuals, which could contribute to an increase in proteolytic activity and a greater damage in lung tissue, thus promoting the development of emphys...
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| Formato: | tesis de maestría |
| Fecha de publicación: | 2018 |
| País: | España |
| Recursos: | Universitat Politècnica de València (UPV) |
| Repositorio: | RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia |
| Idioma: | inglés |
| OAI Identifier: | oai:riunet.upv.es:10251/147056 |
| Acesso em linha: | https://riunet.upv.es/handle/10251/147056 |
| Access Level: | acceso abierto |
| Palavra-chave: | Reactive oxygen species Hypoxia. Neutrophil Alpha 1 antitrypsin deficiency Especies reactivas de oxígeno Neutrófilos Déficit de alfa 1 antitripsina Hipoxia. BIOLOGIA CELULAR Máster Universitario en Biotecnología Biomédica-Màster Universitari en Biotecnologia Biomèdica |
| Resumo: | [EN] The number of neutrophils in the lungs of patients with alpha 1 antitrypsin deficiency (AATD) is significantly higher than in those of healthy individuals, which could contribute to an increase in proteolytic activity and a greater damage in lung tissue, thus promoting the development of emphysema observed in some of the patients. We considered the overall objective of this research project to determine if hypoxia induces the activation of neutrophils in patients with AATD. According to our working hypothesis, tissue hypoxia would produce the activation of neutrophils, with the consequent release to the tissue environment of its proteinase content, which would increase its ability to damage lung tissue. On the other hand, the prolongation of neutrophil half-life caused by hypoxia will increase lung tissue exposure to activated neutrophils, which will contribute to the development of the inflammatory process through the release of inflammatory cytokines. The increase in the number of neutrophils in the lungs will contribute to decrease the local O2 levels, leading to an increase in the reactive oxygen species (ROS) quantity and a situation of oxidative damage in the biomolecules (DNA, lipids and proteins) that will contribute to the development of the damage in the lung tissue. In patients with AATD, the neutrophil-released proteinases and the increase in ROS is not eliminated correctly due to the existence of low plasma levels of alpha 1 antitrypsin (AAT). Based on the working hypothesis, we propose as specific objectives: a) Develop a protocol for a long-term study of the degranulation, oxidative profile, ROS production and gene expression in neutrophils from AATD patients and healthy volunteers. b) The determination of the differences of the previous parameters in neutrophils from healthy volunteers against different phenotypes of patients with AATD. The results show that hypoxia positively affects neutrophils degranulation and produces changes in the oxidative status and gene expression of hypoxia-inducible factors. Despite the targets of the study were pediatric patients from a rare disease and limitations in the number of patients impede the collection of robust data, the goal of creating a protocol for studying degranulation, oxidative damage, and gene expression variations was successfully achieved. |
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