Structure-function relationships in pulmonary surfactant membranes: From biophysics to therapy
ABSTRACT Pulmonary surfactant is an essential lipid-protein complex to maintain an operative respiratory surface at the mammalian lungs. It reduces surface tension at the alveolar air-liquid interface to stabilize the lungs against physical forces operating along the compression-expansion breathing cycles. At the same time, surfactant integrates elements establishing a primary barrier against the entry of pathogens. Lack or deficiencies of the surfactant system are associated with respiratory pathologies, which treatment often includes supplementation with exogenous materials. The present review summarizes current models on the molecular mechanisms of surfactant function, with particular emphasis in its biophysical properties to stabilize the lungs and the molecular alterations connecting impaired surfactant with diseased organs. It also provides a perspective on the current surfactant-based strategies to treat respiratory pathologies. This article is part of a Special Issue entitled: Membrane structure and function: Relevance in the cell's physiology, pathology and therapy.
- SourceAvailable from: Jesus Perez-Gil
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- "SP- B, on the other hand, stabilises the interfacial film and supports the formation of membrane–membrane contacts, providing mechanical stability to the compressed multi-layered films. Upon expansion, SP-B and SP-C are thought to promote insertion and re-spreading of the phospholipids from the reservoirs back into the interface   "
ABSTRACT: To consider the lung as a target for drug delivery and to optimize strategies directed at the pulmonary route, it is essential to consider the role of pulmonary surfactant, a thin lipid-protein film lining the respiratory surface of mammalian lungs. Membrane-based surfactant multilayers are essential for reducing the surface tension at the respiratory air-liquid interface to minimize the work of breathing. Different components of surfactant are also responsible for facilitating the removal of potentially pathological entities such as microorganisms, allergens or environmental pollutants and particles. Upon inhalation, drugs or nanoparticles first contact the surfactant layer, and these interactions critically affect their lifetime and fate in the airways. This review summarizes the current knowledge on the possible role and effects of the pulmonary surfactant system in drug delivery strategies. It also summarizes the evidence that suggests that pulmonary surfactant is far from being an insuperable barrier and could be used as an efficient shuttle for delivering hydrophobic and hydrophilic compounds deep into the lung and the organism. Copyright © 2015. Published by Elsevier B.V.European Journal of Pharmaceutics and Biopharmaceutics 02/2015; DOI:10.1016/j.ejpb.2015.02.014 · 4.25 Impact Factor
- Biophysical Journal 01/2014; 106(2):513a. DOI:10.1016/j.bpj.2013.11.2869 · 3.83 Impact Factor
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ABSTRACT: Inhalation of waterproofing spray products has on several occasions caused lung damage, which in some cases was fatal. The present study aims to elucidate the mechanism of action of a nanofilm spray product, which has been shown to possess unusual toxic effects, including an extremely steep concentration-effect curve. The nanofilm product is intended for application on non-absorbing flooring materials and contains perfluorosiloxane as the active film-forming component. The toxicological effects and their underlying mechanisms of this product were studied using a mouse inhalation model, by in vitro techniques and by identification of the binding interaction. Inhalation of the aerosolised product gave rise to increased airway resistance in the mice, as evident from the decreased expiratory flow rate. The toxic effect of the waterproofing spray product included interaction with the pulmonary surfactants. More specifically, the active film-forming components in the spray product, perfluorinated siloxanes, inhibited the function of the lung surfactant due to non-covalent interaction with surfactant protein B, a component which is crucial for the stability and persistence of the lung surfactant film during respiration. The active film-forming component used in the present spray product is also found in several other products on the market. Hence, it may be expected that these product may have a toxicity similar to the waterproofing product studied here. Elucidation of the toxicological mechanism and identification of toxicological targets are important to perform rational and cost-effective toxicological studied. Thus, since the pulmonary surfactant system appears to be an important toxicological target for waterproofing spray products, study of surfactant inhibition could be included in toxicological assessment of this group of consumer products.Toxicological Sciences 05/2014; DOI:10.1093/toxsci/kfu098 · 4.48 Impact Factor