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Archives of Disease in Childhood. Fetal... Nov 2019Non-invasive ventilation and especially the application of continuous positive airway pressure (CPAP) has become standard for the treatment of premature infants with... (Review)
Review
Non-invasive ventilation and especially the application of continuous positive airway pressure (CPAP) has become standard for the treatment of premature infants with respiratory problems. However, CPAP failure may occur due to respiratory distress syndrome, that is, surfactant deficiency. Less invasive surfactant administration (LISA) aims to provide an adequate dose of surfactant while the infant is breathing spontaneously, thus avoiding positive pressure ventilation support. Using a thin catheter for surfactant application allows infants to maintain function of the glottis and continue spontaneous breathing, whereas the INtubate-SURfactant-Extubate (INSURE) procedure is connected with sedation/analgesia, regular intubation and a (brief) period of positive pressure ventilation. Individual studies and meta-analyses summarised in this review point in the direction that LISA is more effective than standard treatment or INSURE both in terms of short-term (avoidance of mechanical ventilation) and long-term (intracerebral haemorrhage and bronchopulmonary dysplasia) outcomes. Open questions include exact treatment thresholds for different gestational ages, the usefulness of devices/catheters that have recently been purpose-built for the LISA technique and especially the question of analgesia/sedation during the procedure. The current technology still demands laryngoscopy with all its unpleasant effects for infants. Therefore, studies with pharyngeal surfactant deposition immediately after delivery, the use of laryngeal airways for surfactant administration and attempts to nebulise surfactant are under way. Finally, LISA is not simply an isolated technical procedure for surfactant delivery but rather part of a comprehensive non-invasive approach supporting the concept of a gentle transition to the extrauterine world enabling preterm infants to benefit from the advantages of spontaneous breathing.
Topics: Gestational Age; Humans; Infant, Newborn; Infant, Premature; Noninvasive Ventilation; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 31296694
DOI: 10.1136/archdischild-2018-316557 -
Physiological Research Sep 2017The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can... (Review)
Review
The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells and pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation. From immunological point of view, surfactant specific proteins (SPs) SP-A and SP-D are best characterized, however, there is increasing evidence on the involvement of SP-B and SP-C and certain phospholipids in immune reactions. In animal models, the instillation of LPS to the respiratory system induces acute lung injury (ALI). It is of clinical importance that endotoxin-induced lung injury can be favorably influenced by intratracheal instillation of exogenous surfactant. The beneficial effect of this treatment was confirmed for both natural porcine and synthetic surfactants. It is believed that the surfactant preparations have anti-inflammatory properties through regulating cytokine production by inflammatory cells. The mechanism by which LPS interferes with ATII cells and surfactant layer, and its consequences are discussed below.
Topics: Acute Lung Injury; Animals; Biological Products; Humans; Lipopolysaccharides; Lung; Phospholipids; Pulmonary Surfactants; Swine
PubMed: 28937231
DOI: 10.33549/physiolres.933672 -
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 -
Frontiers in Immunology 2022Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism the respiratory surface. The presence of... (Review)
Review
Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism the respiratory surface. The presence of pulmonary surfactant prevents the dissemination of pathogens, modulates immune responses, and optimizes lung biophysical activity. Thus, the application of pulmonary surfactant for the treatment of respiratory diseases provides an effective strategy. Currently, several clinical trials are investigating the use of surfactant preparations to treat patients with coronavirus disease 2019 (COVID-19). Some factors have been considered in the application of pulmonary surfactant for the treatment COVID-19, such as mechanical ventilation strategy, timing of treatment, dose delivered, method of delivery, and preparation utilized. This review supplements this list with two additional factors: accurate measurement of surfactants in patients and proper selection of pulmonary surfactant components. This review provides a reference for ongoing exogenous surfactant trials involving patients with COVID-19 and provides insight for the development of surfactant preparations for the treatment of viral respiratory infections.
Topics: Humans; Lung; Pulmonary Surfactants; Respiration, Artificial; Surface-Active Agents; COVID-19 Drug Treatment
PubMed: 35592339
DOI: 10.3389/fimmu.2022.842453 -
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 -
Cellular & Molecular Biology Letters Nov 2023The pulmonary surfactant that lines the air-liquid surface within alveoli is a protein-lipid mixture essential for gas exchange. Surfactant lipids and proteins are...
BACKGROUND
The pulmonary surfactant that lines the air-liquid surface within alveoli is a protein-lipid mixture essential for gas exchange. Surfactant lipids and proteins are synthesized and stored in the lamellar body (LB) before being secreted from alveolar type II (AT2) cells. The molecular and cellular mechanisms that regulate these processes are incompletely understood. We previously identified an essential role of general control of amino acid synthesis 5 like 1 (GCN5L1) and the biogenesis of lysosome-related organelle complex 1 subunit 1 (BLOS1) in surfactant system development in zebrafish. Here, we explored the role of GCN5L1 in pulmonary surfactant regulation.
METHOD
GCN5L1 knockout cell lines were generated with the CRISPR/Cas9 system. Cell viability was analyzed by MTT assay. Released surfactant proteins were measured by ELISA. Released surfactant lipids were measured based on coupled enzymatic reactions. Gene overexpression was mediated through lentivirus. The RNA levels were detected through RNA-sequencing (RNA-seq) and quantitative reverse transcription (qRT)- polymerase chain reaction (PCR). The protein levels were detected through western blotting. The cellular localization was analyzed by immunofluorescence. Morphology of the lamellar body was analyzed through transmission electron microscopy (TEM), Lysotracker staining, and BODIPY phosphatidylcholine labeling.
RESULTS
Knocking out GCN5L1 in MLE-12 significantly decreased the release of surfactant proteins and lipids. We detected the downregulation of some surfactant-related genes and misregulation of the ROS-Erk-Foxo1-Cebpα axis in mutant cells. Modulating the activity of the axis or reconstructing the mitochondrial expression of GCN5L1 could partially restore the expression of these surfactant-related genes. We further showed that MLE-12 cells contained many LB-like organelles that were lipid enriched and positive for multiple LB markers. These organelles were smaller in size and accumulated in the absence of GCN5L1, indicating both biogenesis and trafficking defects. Accumulated endogenous surfactant protein (SP)-B or exogenously expressed SP-B/SP-C in adenosine triphosphate-binding cassette transporterA3 (ABCA3)-positive organelles was detected in mutant cells. GCN5L1 localized to the mitochondria and LBs. Reconstruction of mitochondrial GCN5L1 expression rescued the organelle morphology but failed to restore the trafficking defect and surfactant release, indicating specific roles associated with different subcellular localizations.
CONCLUSIONS
In summary, our study identified GCN5L1 as a new regulator of pulmonary surfactant that plays a role in the biogenesis and positioning/trafficking of surfactant-containing LBs.
Topics: Animals; Mice; Alveolar Epithelial Cells; Lamellar Bodies; Lipids; Pulmonary Surfactants; RNA; Surface-Active Agents; Zebrafish
PubMed: 37936104
DOI: 10.1186/s11658-023-00506-0 -
Environmental Health Perspectives Apr 1984Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include... (Review)
Review
Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include surfactant composition, cellular and subcellular sites as well as pathways of biosynthesis of phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol. The surfactant system in the developing fetus and neonate is considered in terms of phospholipid content and composition, rates of precursor incorporation, activities of individual enzymes of phospholipid synthesis and glycogen content and metabolism. The influence of the following hormones and other factors on lung maturation and surfactant production is discussed: glucocorticoids, thyroid hormone, estrogen, prolactin, cyclic AMP, beta-adrenergic and cholinergic agonists, prostaglandins and growth factors. The influence of maternal diabetes, fetal sex, stress and labor are also considered. Nonphysiologic and toxic agents which influence surfactant in the fetus, newborn and adult are reviewed.
Topics: Adrenergic beta-Agonists; Animals; Cyclic AMP; Diabetes Mellitus; Estrogens; Female; Fetus; Glucocorticoids; Glycogen; Humans; Lipids; Lung; Parasympathomimetics; Phosphatidic Acids; Phosphatidylcholines; Phosphatidylglycerols; Pregnancy; Prolactin; Prostaglandins; Pulmonary Surfactants; Subcellular Fractions; Thyrotropin-Releasing Hormone
PubMed: 6145585
DOI: 10.1289/ehp.8455205 -
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 -
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 -
Microbes and Infection Jan 2012Pulmonary surfactant is a complex surface-active substance comprised of key phospholipids and proteins that has many essential functions. Surfactant's unique composition... (Review)
Review
Pulmonary surfactant is a complex surface-active substance comprised of key phospholipids and proteins that has many essential functions. Surfactant's unique composition is integrally related to its surface-active properties, its critical role in host defense, and emerging immunomodulatory activities ascribed to surfactant lipids. Together these effector functions provide for lung stability and protection from a barrage of potentially virulent infectious pathogens.
Topics: Animals; Communicable Diseases; Humans; Immunologic Factors; Lung Diseases; Pulmonary Surfactants
PubMed: 21945366
DOI: 10.1016/j.micinf.2011.08.019