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Pulmonary surfactant-related factors in the pathogenesis and therapies of respiratory diseases

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2021-08-31
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Universidad Complutense de Madrid
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Respiratory diseases are one of the primary causes of death, disability and health costs worldwide. In this framework, the lack and dysfunction of lung surfactant may result in airless collapsed alveoli and difficulty for breathing, being the primary trigger or a contributing factor of severe respiratory disorders, such as neonatal respiratory distress syndrome (RDS) and acute respiratory distress syndrome (ARDS). RDS is a common cause of morbidity in preterm neonates, associated to immature lungs and an impaired secretion of pulmonary surfactant. The latter is, instead, present but inactivated during ARDS, a quickly progressive severe respiratory failure characterised by widespread acute lung inflammation. In both diseases, the leading role of pulmonary surfactant is due to its specific properties, which permit to maintain reduced surface tension values at the alveolar spaces, particularly upon exhalation. To accomplish this function, its lipid-protein complexes are secreted by pneumocyte type II cells and distribute, as a dense network of membranes, at the air liquid-interface that is generated between the aqueous layer covering the pulmonary epithelium and the alveolar air space. The resulting efficient adsorption, spreading and reorganisation of lung surfactant prevent alveolar collapse and depend on its particular composition: ~90% lipids, mainly disaturated phospholipids (~50%), and 10% of hydrophilic (SP-A and SP-D) and highly hydrophobic proteins (SP-B and SP-C)...
Las enfermedades respiratorias son una de las principales causas de muerte, discapacidad y gasto sanitario en todo el mundo. En este contexto, la falta o disfunción del surfactante pulmonar puede ser el desencadenante principal o un factor contribuyente de trastornos respiratorios graves, como el síndrome de dificultad respiratoria neonatal (RDS) y el síndrome de dificultad respiratoria aguda (ARDS). Gracias a su composición, estructura y actividad interfacial, el surfactante pulmonar cumple una función vital durante el proceso de la respiración, reduciendo la tensión superficial del fluido alveolar y minimizando la energía necesaria especialmente durante la exhalación. Aproximadamente el 90% del surfactante pulmonar son lípidos, principalmente fosfolípidos disaturados (~ 50%). El 10% restante lo componen fundamentalmente proteínas, dos hidrofílicas (SP-A y SP-D) y otras dos altamente hidrofóbicas (SP-B y SP-C). Para lograr esta función vital, los complejos lipoproteícos del surfactante se distribuyen como una densa red de membranas en la interfase aire-líquido generada entre la capa acuosa que recubre el epitelio pulmonar y el espacio aéreo alveolar. El resultado es una eficiente adsorción, propagación y reorganización del material tensoactivo que previene el colapso alveolar...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Bioquímica y Biología Molecular, leída el 19-04-2021
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