Molecular mechanisms in the biogenesis of surface-active lung surfactant complexes
The pulmonary surfactant is a lipid/protein complex that diminishes surface tension forces and facilitates respiratory dynamics upon coating the alveolar air-liquid interface. This surfaceactive agent is synthesized by specialized cells of the alveolar epithelium termed type II pneumocytes. The synt...
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| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/11660 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/11660 |
| Access Level: | acceso abierto |
| Palabra clave: | 661.185(043.2) Lung surfactant Pulmonary surfactant Surface-active complexes Surfactant complexes Surfactante pulmonar Complejos tensioactivos Biotecnología Bioquímica (Biología) 3399 Otras Especialidades Tecnológicas 2302 Bioquímica |
| Sumario: | The pulmonary surfactant is a lipid/protein complex that diminishes surface tension forces and facilitates respiratory dynamics upon coating the alveolar air-liquid interface. This surfaceactive agent is synthesized by specialized cells of the alveolar epithelium termed type II pneumocytes. The synthesis of lung surfactant is a highly regulated biological process involving, not only synthesis and maturation of surfactant proteins, but also lipid packing and assembly. Its biogenesis leads to the formation of tightly packed multilamellar organelles calledlamellar bodies. In the recent years, several studies have suggested that freshly secreted lung surfactant complexes have particular structural properties leading to a highly active interfacial behaviour. However, surfactant complexes used typically in both research and clinical applications are usually isolated from lavages of animal lungs and have already gone through structural alterations as a result of exposure to respiratory dynamics and highly oxidative environments, and scarcely contain freshly assembled surfactant complexes. Notwithstanding evidence, there is not a detailed characterization of the structural and functional differences between a surfactant assembled as lamellar body-like particles and a material already subjected to respiratory dynamics. The reason is the necessary use of cell cultures of type II pneumocytes as the main approach to obtain lamellar bodies, what limits its experimental use. Therefore, the main objective of this Thesis is to describe the molecular determinants underlaying structure-function relationships of lung surfactant complexes with similar properties to freshly secreted surfactant aggregates packed as highly dehydrated and particularly active lamellar bodies... |
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