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Biochimica Et Biophysica Acta.... Jun 2022Pulmonary surfactant is a mixture of lipids and proteins, consisting of 90% phospholipid, and 10% protein by weight, found predominantly in pulmonary alveoli of... (Review)
Review
Pulmonary surfactant is a mixture of lipids and proteins, consisting of 90% phospholipid, and 10% protein by weight, found predominantly in pulmonary alveoli of vertebrate lungs. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), are present within the alveoli at very high concentrations, and exert anti-inflammatory effects by regulating multiple Toll like receptors (TLR2/1, TLR4, and TLR2/6) by antagonizing cognate ligand-dependent activation. POPG also attenuates LPS-induced lung injury in vivo. In addition, these lipids bind directly to RSV and influenza A viruses (IAVs) and block interaction between host cells and virions, and thereby prevent viral replication in vitro. POPG and PI also inhibit RSV and IAV infection in vivo, in mice and ferrets. The lipids markedly inhibit SARS-CoV-2 infection in vitro. These findings suggest that both POPG and PI have strong potential to be applied as both prophylaxis and post-infection treatments for problematic respiratory viral infections.
Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Ferrets; Lung; Mice; Phospholipids; Pulmonary Surfactants; SARS-CoV-2; Toll-Like Receptor 2; COVID-19 Drug Treatment
PubMed: 35240310
DOI: 10.1016/j.bbalip.2022.159139 -
Biochimica Et Biophysica Acta.... Sep 2017Pulmonary surfactant is a membrane-based lipid-protein system essential for the process of breathing, which coats and stabilizes the whole respiratory surface and... (Review)
Review
Pulmonary surfactant is a membrane-based lipid-protein system essential for the process of breathing, which coats and stabilizes the whole respiratory surface and possesses exceptional biophysical properties. It constitutes the first barrier against the entry of pathogens and harmful particles in the alveolar region, extended through the lungs, but on the other hand, it can offer novel possibilities as a shuttle for the delivery of drugs and nanocarriers. The advances in nanotechnology are opening the doors to new diagnostic and therapeutic avenues, which are not accessible by means of the current approaches. In this context, the pulmonary route is called to become a powerful way of entry for innovative treatments based on nanotechnology. In this review, the anatomy of the respiratory system and its properties for drug entry are first revisited, as well as some current strategies that use the respiratory route for both local and peripheral action. Then, a brief overview is presented on what pulmonary surfactant is, how it works and why it could be used as a drug delivery vehicle. Finally, the review is closed with a description of the development of nanocarriers in the lung context and their interaction with endogenous and clinical pulmonary surfactants. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.
Topics: Drug Delivery Systems; Humans; Hydrophobic and Hydrophilic Interactions; Nanomedicine; Nanoparticles; Particle Size; Pulmonary Surfactants
PubMed: 28450046
DOI: 10.1016/j.bbamem.2017.04.019 -
Biochimica Et Biophysica Acta Oct 2016Lung surfactant lines the gas-exchange interface in the lungs and reduces the surface tension, which is necessary for breathing. Lung surfactant consists mainly of... (Review)
Review
Lung surfactant lines the gas-exchange interface in the lungs and reduces the surface tension, which is necessary for breathing. Lung surfactant consists mainly of lipids with a small amount of proteins and forms a monolayer at the air-water interface connected to bilayer reservoirs. Lung surfactant function involves transfer of material between the monolayer and bilayers during the breathing cycle. Lipids and proteins are organized laterally in the monolayer; selected species are possibly preferentially transferred to bilayers. The complex 3D structure of lung surfactant and the exact roles of lipid organization and proteins remain important goals for research. We review recent simulation studies on the properties of lipid monolayers, monolayers with phase coexistence, monolayer-bilayer transformations, lipid-protein interactions, and effects of nanoparticles on lung surfactant. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.
Topics: Computer Simulation; Lipid Bilayers; Membrane Lipids; Membrane Proteins; Nanoparticles; Pulmonary Surfactants; Surface Tension
PubMed: 26922885
DOI: 10.1016/j.bbamem.2016.02.030 -
European Journal of Pharmaceutics and... Sep 2015To consider the lung as a target for drug delivery and to optimise strategies directed at the pulmonary route, it is essential to consider the role of pulmonary... (Review)
Review
To consider the lung as a target for drug delivery and to optimise 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 minimise 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 summarises the current knowledge on the possible role and effects of the pulmonary surfactant system in drug delivery strategies. It also summarises 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.
Topics: Administration, Inhalation; Animals; Drug Carriers; Drug Delivery Systems; Humans; Hydrophobic and Hydrophilic Interactions; Lung; Pulmonary Surfactants; Surface Tension
PubMed: 25709061
DOI: 10.1016/j.ejpb.2015.02.014 -
European Journal of Pediatrics Aug 2020Preterm neonates with respiratory distress syndrome (RDS) are commonly treated with surfactant by intubate surfactant extubate (InSurE) technique. Mode of surfactant... (Comparative Study)
Comparative Study Randomized Controlled Trial
Minimally invasive surfactant therapy versus InSurE in preterm neonates of 28 to 34 weeks with respiratory distress syndrome on non-invasive positive pressure ventilation-a randomized controlled trial.
Preterm neonates with respiratory distress syndrome (RDS) are commonly treated with surfactant by intubate surfactant extubate (InSurE) technique. Mode of surfactant administration has evolved towards less invasive technique in the last few years. We randomised 58 preterm infants of 28-34 weeks of gestation with RDS within 6 h of birth to receive surfactant by InSurE or minimally invasive surfactant therapy (MIST). Non-invasive positive pressure ventilation (NIPPV) was used as primary respiratory support. The main objective was to compare the need of invasive mechanical ventilation (IMV) in first 72 h of life and secondarily hemodynamically significant patent ductus arteriosus (hsPDA), intraventricular haemorrhage (IVH) (> grade 2), bronchopulmonary dysplasia (BPD) and composite outcome of BPD/mortality. We did not find any difference in need of IMV in first 72 h between MIST and InSurE (relative risk with MIST, 0.62; 95% confidence interval, 0.22 to 1.32). No difference was observed in terms of hs PDA, IVH (> grade 2), BPD and composite outcome of BPD/mortality.Conclusion: There is no difference between MIST and InSurE in preterm neonates with RDS with NIPPV as a primary mode of respiratory support. Larger multicentre studies are needed to further explore differences in treatment failure and other secondary outcomes.Trial registration: www.ctri.nic.in id CTRI/2019/03/017992, registration date March 8, 2019. What is Known • InSurE is commonly used for many years for treatment of RDS in preterm neonates. • MIST has been introduced as a newer tool. What is New • MIST with feeding tube is comparable with InSurE in preterm infants with RDS in developing countries. •NIPPV can be used as primary respiratory support for MIST.
Topics: Combined Modality Therapy; Female; Humans; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Male; Noninvasive Ventilation; Positive-Pressure Respiration; Prospective Studies; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Treatment Outcome
PubMed: 32462483
DOI: 10.1007/s00431-020-03682-9 -
Colloids and Surfaces. B, Biointerfaces Feb 2022Pulmonary fungal infections lead to damage of the endogenous lung surfactant system. However, the molecular mechanism underlying surfactant inhibition is unknown....
Pulmonary fungal infections lead to damage of the endogenous lung surfactant system. However, the molecular mechanism underlying surfactant inhibition is unknown. β-D-glucan is the major component of pathogenic fungal cell walls and is also present in organic dust, which increases the risk of respiratory diseases. The objective of this study was to characterize the interaction of this D-glucopyranose polymer with pulmonary surfactant. Our results show that β-D-glucan induced a concentration-dependent inhibition of the surface adsorption, respreading, and surface tension-lowering activity of surfactant preparations containing surfactant proteins SP-B and SP-C. Our data support a new mechanism of surfactant inhibition that consists in the extraction of phospholipid molecules from surfactant membranes by β-D-glucan. As a result, surfactant membranes became more fluid, as demonstrated by fluorescence anisotropy, and showed decreased T and transition enthalpy. Surfactant preparations containing surfactant protein A (SP-A) were more resistant to β-D-glucan inhibition. SP-A bound to different β-D-glucans with high affinity (K = 1.5 ± 0.1 nM), preventing and reverting β-D-glucan inhibitory effects on surfactant interfacial adsorption and partially abrogating β-D-glucan inhibitory effects on surfactant's reduction of surface tension. We conclude that β-D-glucan inhibits the biophysical function of surfactant preparations lacking SP-A by subtraction of phospholipids from surfactant bilayers and monolayers. The increased resistance of SP-A-containing surfactant preparations to β-D-glucan reinforces its use in surfactant replacement therapy.
Topics: Glucans; Phospholipids; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactants
PubMed: 34836708
DOI: 10.1016/j.colsurfb.2021.112237 -
Immunological Reviews Aug 2023The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the... (Review)
Review
The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the innate immune system in the lung. Pulmonary surfactant is a lipoprotein complex consisting of 90% phospholipids and 10% protein, by weight. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), exist at very high concentrations in the extracellular alveolar compartments. We have reported that one of the most dominant molecular species of PG, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and PI inhibit inflammatory responses induced by multiple toll-like receptors (TLR2/1, TLR3, TLR4, and TLR2/6) by interacting with subsets of multiprotein receptor components. These lipids also exert potent antiviral effects against RSV and influenza A, in vitro, by inhibiting virus binding to host cells. POPG and PI inhibit these viral infections in vivo, in multiple animal models. Especially noteworthy, these lipids markedly attenuate SARS-CoV-2 infection including its variants. These lipids are natural compounds that already exist in the lung and, thus, are less likely to cause adverse immune responses by hosts. Collectively, these data demonstrate that POPG and PI have strong potential as novel therapeutics for applications as anti-inflammatory compounds and preventatives, as treatments for broad ranges of RNA respiratory viruses.
Topics: Animals; Humans; Phospholipids; Pulmonary Surfactants; Antiviral Agents; Toll-Like Receptor 2; COVID-19; SARS-CoV-2; Lung; Anti-Inflammatory Agents; Phosphatidylglycerols
PubMed: 37144896
DOI: 10.1111/imr.13207 -
Archives of Disease in Childhood. Fetal... Jul 2023
Topics: Humans; Infant, Newborn; Surface-Active Agents; Pulmonary Surfactants; Infant, Premature; Neonatology; Respiratory Distress Syndrome, Newborn
PubMed: 37185271
DOI: 10.1136/archdischild-2022-325061 -
Advances in Colloid and Interface... Oct 2020Particulate matter (PM), which is the primary contributor to air pollution, has become a pervasive global health threat. When PM enters into a respiratory tract, the... (Review)
Review
Particulate matter (PM), which is the primary contributor to air pollution, has become a pervasive global health threat. When PM enters into a respiratory tract, the first body tissues to be directly exposed are the cells of respiratory tissues and pulmonary surfactant. Pulmonary surfactant is a pivotal component to modulate surface tension of alveoli during respiration. Many studies have proved that PM would interact with pulmonary surfactant to affect the alveolar activity, and meanwhile, pulmonary surfactant would be adsorbed to the surface of PM to change the toxic effect of PM. This review focuses on recent studies of the interactions between micro/nanoparticles (synthesized and environmental particles) and pulmonary surfactant (natural surfactant and its models), as well as the health effects caused by PM through a few significant aspects, such as surface properties of PM, including size, surface charge, hydrophobicity, shape, chemical nature, etc. Moreover, in vitro and in vivo studies have shown that PM leads to oxidative stress, inflammatory response, fibrosis, and cancerization in living bodies. By providing a comprehensive picture of PM-surfactant interaction, this review will benefit both researchers for further studies and policy-makers for setting up more appropriate regulations to reduce the adverse effects of PM on public health.
Topics: Animals; Health; Humans; Nanoparticles; Particulate Matter; Pulmonary Surfactants
PubMed: 32871405
DOI: 10.1016/j.cis.2020.102244 -
International Journal of Molecular... Jul 2023The alveolar epithelium is covered by a non-cellular layer consisting of an aqueous hypophase topped by pulmonary surfactant, a lipo-protein mixture with surface-active... (Review)
Review
The alveolar epithelium is covered by a non-cellular layer consisting of an aqueous hypophase topped by pulmonary surfactant, a lipo-protein mixture with surface-active properties. Exposure to cigarette smoke (CS) affects lung physiology and is linked to the development of several diseases. The macroscopic effects of CS are determined by several types of cell and molecular dysfunction, which, among other consequences, lead to surfactant alterations. The purpose of this review is to summarize the published studies aimed at uncovering the effects of CS on both the lipid and protein constituents of surfactant, discussing the molecular mechanisms involved in surfactant homeostasis that are altered by CS. Although surfactant homeostasis has been the topic of several studies and some molecular pathways can be deduced from an analysis of the literature, it remains evident that many aspects of the mechanisms of action of CS on surfactant homeostasis deserve further investigation.
Topics: Pulmonary Surfactants; Electronic Nicotine Delivery Systems; Surface-Active Agents; Nicotiana; Lung
PubMed: 37511463
DOI: 10.3390/ijms241411702