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Chemical Reviews Dec 2023Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing... (Review)
Review
Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorption-driven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compression-driven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.
Topics: Infant, Newborn; Humans; Pulmonary Surfactants; Phospholipids; Surface-Active Agents; Surface Tension; Chemical Phenomena
PubMed: 37862151
DOI: 10.1021/acs.chemrev.3c00146 -
Canadian Journal of Biochemistry and... Nov 1984The mammalian lung is stabilized by a specialized material, the pulmonary surfactant, which acts by reversibly reducing the surface tension at the air-liquid interface... (Review)
Review
The mammalian lung is stabilized by a specialized material, the pulmonary surfactant, which acts by reversibly reducing the surface tension at the air-liquid interface of the lung during breathing. Pulmonary surfactant contains approximately 90% lipid and 10% proteins. Dipalmitoyl phosphatidylcholine, the major lipid component, appears to be primarily responsible for the ability to reduce surface tension to near 0 dyn/cm (1 dyn = 10 microN). The other components of pulmonary surfactant promote the adsorption and spreading of this disaturated lecithin at the air-liquid interface. Surfactant activity can be accessed by physical and biological assays. Apparent discrepancies between the results obtained with the Wilhelmy plate surface balance and the pulsating bubble surfactometer have led to the suggestion that separate "protein-facilitated" (catalytic type) and "protein-mediated" (chemical type) processes may be involved in adsorption and (or) spreading at the different surfactant concentrations used with these two techniques. Artificial surfactants, which mimic the essential properties of the natural product with the pulsating bubble surfactometer, can be produced with synthetic lipids. Treatment of prematurely delivered infants suffering from the neonatal respiratory distress syndrome with lipid extracts of pulmonary surfactant leads to a marked improvement in gaseous exchange.
Topics: Animals; Female; Fetus; Humans; Infant, Newborn; Lung; Models, Biological; Pregnancy; Pressure; Proteins; Pulmonary Alveoli; Pulmonary Surfactants; Respiration; Surface Properties; Surface Tension
PubMed: 6395944
DOI: 10.1139/o84-146 -
Annual Review of Medicine 1989Pulmonary surfactant is a chemically heterogeneous material that provides a stable, low surface tension within the lung, thereby preventing alveolar collapse at low... (Review)
Review
Pulmonary surfactant is a chemically heterogeneous material that provides a stable, low surface tension within the lung, thereby preventing alveolar collapse at low transpulmonary pressures. Both the lipid and the protein components of surfactant are important for establishing and maintaining a low surface tension. The composition of surfactant, the biogenesis of surfactant components, and the biologic roles of surfactant components are discussed in this brief review. Surfactant functions in adult lung disease and surfactant replacement therapy are also briefly considered.
Topics: Animals; Humans; Infant, Newborn; Pulmonary Surfactants; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Surface Tension
PubMed: 2658759
DOI: 10.1146/annurev.me.40.020189.002243 -
Journal of Applied Physiology:... Jul 1982Pulmonary surfactant reduces the surface tension of the alveolar air-liquid interface, thereby providing mechanical stability and preventing alveolar atelectasis. More... (Review)
Review
Pulmonary surfactant reduces the surface tension of the alveolar air-liquid interface, thereby providing mechanical stability and preventing alveolar atelectasis. More than 50% of surfactant is dipalmitoyl phosphatidylcholine, a material that is capable of reducing the surface tension of the alveolar interface to uniquely low values. The functions of the remaining 25% unsaturated phosphatidylcholines, 5-10% phosphatidylglycerol, 5% cholesterol, and 8-10% protein are unknown. Surfactant is synthesized by alveolar epithelial type II cells and is probably secreted as a lipoprotein complex. Lamellar bodies, which distinguish type II cells, are likely to be intracellular sites of transport of processing. The catabolism of surfactant after it is secreted into the alveolar lumen is complicated and involves different turnover times for the phosphatidylcholines, phosphatidylglycerol, and the proteins. The metabolic events are under hormonal control and may involve an interplay between beta-adrenergic agonists cAMP, and prostaglandins. In disease, such as the neonatal and adult respiratory distress syndromes, derangements in the metabolic processes may produce surfactant that is abnormal with respect to its chemical and physical properties.
Topics: Adult; Animals; Apolipoproteins; Fetus; Humans; Infant, Newborn; Lung; Phosphatidylcholines; Phosphatidylglycerols; Pulmonary Surfactants; Rabbits; Respiration
PubMed: 6749772
DOI: 10.1152/jappl.1982.53.1.1 -
The Journal of Biological Chemistry Oct 1994
Review
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Pulmonary Surfactants
PubMed: 7929300
DOI: No ID Found -
The New England Journal of Medicine Mar 1993
Clinical Trial Review
Topics: Humans; Infant, Newborn; Lung; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 8441430
DOI: 10.1056/NEJM199303253281208 -
Biomedical Journal Aug 2022The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement... (Review)
Review
The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement therapies (SRT). It took some time to close the gap between the identification of the biophysical and molecular causes of the high mortality associated with respiratory distress syndrome in very premature babies and the development of a proper therapy. Closing the gap required the elucidation of some key questions defining the structure-function relationships in surfactant as well as the particular role of the different molecular components assembled into the surfactant system. On the other hand, the application of SRT as part of treatments targeting other devastating respiratory pathologies, in babies and adults, is depending on further extensive research still required before enough amounts of good humanized clinical surfactants will be available. This review summarizes our current concepts on the compositional and structural determinants defining pulmonary surfactant activity, the principles behind the development of efficient natural animal-derived or recombinant or synthetic therapeutic surfactants, as well as a the most promising lines of research that are already opening new perspectives in the application of tailored surfactant therapies to treat important yet unresolved respiratory pathologies.
Topics: Animals; Humans; Infant, Newborn; Pulmonary Surfactants; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 35272060
DOI: 10.1016/j.bj.2022.03.001 -
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 -
International Journal of Molecular... Dec 2022Diffuse parenchymal lung diseases (DPLD) or Interstitial lung diseases (ILD) are a heterogeneous group of lung conditions with common characteristics that can progress... (Review)
Review
Diffuse parenchymal lung diseases (DPLD) or Interstitial lung diseases (ILD) are a heterogeneous group of lung conditions with common characteristics that can progress to fibrosis. Within this group of pneumonias, idiopathic pulmonary fibrosis (IPF) is considered the most common. This disease has no known cause, is devastating and has no cure. Chronic lesion of alveolar type II (ATII) cells represents a key mechanism for the development of IPF. ATII cells are specialized in the biosynthesis and secretion of pulmonary surfactant (PS), a lipid-protein complex that reduces surface tension and minimizes breathing effort. Some differences in PS composition have been reported between patients with idiopathic pulmonary disease and healthy individuals, especially regarding some specific proteins in the PS; however, few reports have been conducted on the lipid components. This review focuses on the mechanisms by which phospholipids (PLs) could be involved in the development of the fibroproliferative response.
Topics: Humans; Pulmonary Surfactants; Phospholipids; Lung; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial
PubMed: 36613771
DOI: 10.3390/ijms24010326 -
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