Compositional, structural and functional properties of discrete coexisting complexes within bronchoalveolar pulmonary surfactant

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Castillo Sánchez, José Carlos and Cerrada, Alejandro and Conde, Mikel and Cruz Rodríguez, Antonio and Pérez Gil, Jesús (2021) Compositional, structural and functional properties of discrete coexisting complexes within bronchoalveolar pulmonary surfactant. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1864 (183808). pp. 1-11. ISSN 0005-2736

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Official URL: https://doi.org/10.1016/j.bbamem.2021.183808



Abstract

Lung surfactant (LS) stabilizes the respiratory surface by forming a film at the alveolar air-liquid interface that reduces surface tension and minimizes the work of breathing. Typically, this surface-active agent has been isolated from animal lungs both for research and biomedical applications. However, these materials are constituted by complex membranous architectures including surface-active and inactive lipid/protein assemblies. In this work, we describe the composition, structure and surface activity of discrete membranous entities that are part of a LS preparation isolated from bronchoalveolar lavages of porcine lungs. Seven different fractions could be resolved from whole surfactant subjected to sucrose density gradient centrifugation. Detailed compositional characterization revealed differences in protein and cholesterol content but no distinct saturated:unsaturated phosphatidylcholine ratios. Moreover, no significant differences were detected regarding apparent hydration at the headgroup region of membranes, as reported by the probe Laurdan, and lipid chain mobility analysed by electron spin resonance (ESR) in spite of the variety of membranous assemblies observed by transmission electron microscopy. In addition, six of the seven separated LS subfractions formed similar, essentially disordered-like, interfacial films and performed efficient surface activity, under physiologically relevant conditions. Altogether, our work show that a LS isolated from porcine lungs is comprised by a heterogenous population of membranous assemblies lacking freshly secreted unused LS complexes sustaining highly dehydrated and ordered membranous assemblies as previously reported. We propose that surfactant subfractions may illustrate intermediates in sequential structural steps within the structural transformations occurring along the respiratory compression-expansion cycles.

Resumen (otros idiomas)

El surfactante pulmonar es un complejo lípido-proteico secretado por el epitelio alveolar a los espacios respiratorios y cuya principal función es formar películas en la interfase aire-líquido que reducen la tensión superficial y así facilitan la mecánica respiratoria. Los complejos se ensamblan en forma de membranas altamente empaquetadas por parte de los neumocitos, que una vez secretadas sufren una serie de transformaciones hasta llegar a la interfase. Posteriormente, y tras ser expuestos al ambiente altamente oxidante de los pulmones, y sometidos a la exigente mecánica de los ciclos de inspiración-espiración, son reciclados e integrados en nuevos complejos o degradados por parte de los macrófagos alveolares. En este trabajo, integrado en la Tesis Doctoral de José Carlos Castillo y con la participación de Mikel Conde como estudiante de TFG, hemos conseguido separar el surfactante completo que se obtiene mediante los lavados broncoalveolares de pulmones animales, en 7 fracciones perfectamente definidas en función de su densidad. Estas 7 fracciones tienen estructura, composición y comportamientos biofísicos bien diferenciados, a partir de los cuales se concluye que pertenecen a diferentes etapas en el metabolismo extracelular de los complejos de surfactante. Ello abre nuevas posibilidades en el estudio de las interacciones y los mecanismos que definen estos procesos, algo esencial para poder ensamblar preparaciones de surfactante exógeno completamente operativas que puedan ser utilizadas en tratamientos terapéuticos.

Item Type:Article
Uncontrolled Keywords:Lung surfactant; Air-liquid interface; Respiratory dynamics; Membrane structure; DSCESR
Subjects:Medical sciences > Biology > Biochemistry
ID Code:73618
Deposited On:15 Jul 2022 13:37
Last Modified:02 Aug 2022 11:00

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