Surfactant protein B (SP-B) is essential in transferring surface-active phospholipids from membrane-based surfactant complexes into the alveolar air-liquid interface. This allows maintaining the mechanical stability of the surfactant film under high pressure at the end of expiration; therefore, SP-B is crucial in lung function. Despite its necessity, the structure and the mechanism of lipid transfer by SP-B have remained poorly characterized. Earlier, we proposed higher-order oligomerization of SP-B into ring-like supramolecular assemblies. In the present work, we used coarse-grained molecular dynamics simulations to elucidate how the ring-like oligomeric structure of SP-B determines its membrane binding and lipid transfer. In particular, we explored how SP-B interacts with specific surfactant lipids, and how consequently SP-B reorganizes its lipid environment to modulate the pulmonary surfactant structure and function. Based on these studies, there are specific lipid-protein interactions leading to perturbation and reorganization of pulmonary surfactant layers. Especially, we found compelling evidence that anionic phospholipids and cholesterol are needed or even crucial in the membrane binding and lipid transfer function of SP-B. Also, on the basis of the simulations, larger oligomers of SP-B catalyze lipid transfer between adjacent surfactant layers. Better understanding of the molecular mechanism of SP-B will help in the design of therapeutic SP-B-based preparations and novel treatments for fatal respiratory complications, such as the acute respiratory distress syndrome.

• Klíčová slova
• SP-B, molecular dynamics simulation, protein–lipid interactions, pulmonary surfactant,
• MeSH
• fosfolipidy chemie   MeSH
• konformace proteinů MeSH
• lipidové dvojvrstvy chemie   metabolismus   MeSH
• molekulární modely MeSH
• multimerizace proteinu MeSH
• plicní surfaktanty chemie   MeSH
• protein B asociovaný s plicním surfaktantem chemie   metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfolipidy MeSH
• lipidové dvojvrstvy MeSH
• plicní surfaktanty MeSH
• protein B asociovaný s plicním surfaktantem MeSH

The lining of the alveoli is covered by pulmonary surfactant, a complex mixture of surface-active lipids and proteins that enables efficient gas exchange between inhaled air and the circulation. Despite decades of advancements in the study of the pulmonary surfactant, the molecular scale behavior of the surfactant and the inherent role of the number of different lipids and proteins in surfactant behavior are not fully understood. The most important proteins in this complex system are the surfactant proteins SP-B and SP-C. Given this, in this work we performed nonequilibrium all-atom molecular dynamics simulations to study the interplay of SP-B and SP-C with multicomponent lipid monolayers mimicking the pulmonary surfactant in composition. The simulations were complemented by z-scan fluorescence correlation spectroscopy and atomic force microscopy measurements. Our state-of-the-art simulation model reproduces experimental pressure-area isotherms and lateral diffusion coefficients. In agreement with previous research, the inclusion of either SP-B and SP-C increases surface pressure, and our simulations provide a molecular scale explanation for this effect: The proteins display preferential lipid interactions with phosphatidylglycerol, they reside predominantly in the lipid acyl chain region, and they partition into the liquid expanded phase or even induce it in an otherwise packed monolayer. The latter effect is also visible in our atomic force microscopy images. The research done contributes to a better understanding of the roles of specific lipids and proteins in surfactant function, thus helping to develop better synthetic products for surfactant replacement therapy used in the treatment of many fatal lung-related injuries and diseases.

• MeSH
• biofyzikální jevy MeSH
• fosfolipidy chemie   MeSH
• plicní surfaktanty * chemie   MeSH
• povrchově aktivní látky MeSH
• povrchové vlastnosti MeSH
• protein B asociovaný s plicním surfaktantem chemie   MeSH
• protein C asociovaný s plicním surfaktantem chemie   MeSH
• proteiny MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfolipidy MeSH
• plicní surfaktanty * MeSH
• povrchově aktivní látky MeSH
• protein B asociovaný s plicním surfaktantem MeSH
• protein C asociovaný s plicním surfaktantem MeSH
• proteiny MeSH

The interaction between exogenous surfactant and various modes of ventilatory support in terms of timing, quality and quantity can influence both short- and long-term outcomes of immature infants. Alterations to the pulmonary surfactant system can occur with all forms of mechanical ventilation. Experimental data suggest possible interaction between ventilatory support and exogenous surfactant even during the first breaths in the delivery room. The adverse effect on surfactant function at this time can increase the need for and duration of ventilatory support. The logical approach to ventilatory support is to be minimally aggressive with optimal recruitment of the lungs to avoid ventilator-induced lung injury. Nasal continuous positive airway pressure (CPAP) in combination with early prophylactic surfactant administration may be an effective and less damaging method capable of reducing the need of artificial ventilation, but its benefit has not been proven in extremely preterm infants less than 28 weeks' gestation. Because of unproven efficacy of nasal CPAP in extremely premature infants, the population most at risk for adverse pulmonary and neurologic outcome, this paper focuses on the comparison of conventional and high-frequency oscillatory ventilation (HFOV) with respect to alteration of surfactant function, and short- and long-term outcomes, in both human and experimental trials. Though the two most recent large clinical trials provide reassurance with respect to the safety of first-intention high-frequency ventilation, the reduction in the risk of chronic lung disease appears to be only modest or absent. Recent laboratory investigations suggest that the key element of HFOV, namely optimization of volume, can, under some circumstances, be replicated with low tidal volume conventional ventilation and high positive end-expiratory pressure. Recent introduction of patient-triggered volume-targeted conventional ventilation into clinical practice offers the promise of a practical means of providing gentle conventional ventilation capable of minimizing ventilator-induced lung injury. Ultimately, well-designed comparative clinical trials with long-term outcomes are essential to accurately quantify risks and benefits of any new approach to mechanical ventilation. Without such data, these experimental results should not be extrapolated into clinical practice, because of the multifactorial pathophysiology of the development of chronic pulmonary disease in extremely premature infants and the risk of unanticipated adverse effects.

• MeSH
• bronchopulmonální dysplazie epidemiologie   etiologie   MeSH
• časové faktory MeSH
• gestační stáří MeSH
• lidé MeSH
• novorozenec MeSH
• plicní surfaktanty aplikace a dávkování   MeSH
• poškození plic MeSH
• trvalý přetlak v dýchacích cestách MeSH
• umělé dýchání metody   MeSH
• výsledek terapie MeSH
• vysokofrekvenční ventilace MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• srovnávací studie MeSH
• Názvy látek
• plicní surfaktanty MeSH

By reducing the surface tension of the air-water interface in alveoli, lung surfactant (LS) is crucial for proper functioning of the lungs. It also forms the first barrier against inhaled pathogens. In this study we inspect the interactions of LS models with a dangerous air pollutant, benzo[a]pyrene (BaP). Dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-oleoylphosphatidylcholine, and their 1:1 mixture are used as LS models. Pressure-area isotherms are employed to study macroscopic properties of the monolayers. We find that addition of BaP has a condensing effect, manifested by lowering the values of surface pressure and shifting the isotherms to smaller areas. Atomistic details of this process are examined by means of molecular dynamics simulations. We show that initially BaP molecules are accumulated in the monolayers. Upon compression, they are forced to the headgroups region and eventually expelled to the subphase. BaP presence results in reduction of monolayer hydration in the hydrophilic region. In the hydrophobic region it induces increased chain ordering, reduction of monolayer fluidity, and advances transition to the liquid condensed phase in the DPPC system.

• Klíčová slova
• air pollution, benzo[a]pyrene, lung surfactant, molecular dynamics, surface pressure-area isotherms,
• MeSH
• 1,2-dipalmitoylfosfatidylcholin analogy a deriváty   chemie   farmakologie   MeSH
• benzopyren chemie   MeSH
• fosfatidylcholiny chemie   MeSH
• plicní alveoly chemie   fyziologie   MeSH
• plicní surfaktanty MeSH
• povrchové napětí MeSH
• simulace molekulární dynamiky MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1-palmitoyl-2-oleoylphosphatidylcholine MeSH Prohlížeč
• 1,2-dipalmitoylfosfatidylcholin MeSH
• benzopyren MeSH
• colfosceril palmitate MeSH Prohlížeč
• fosfatidylcholiny MeSH
• plicní surfaktanty MeSH

Additives in vaping products, such as flavors, preservatives, or thickening agents, are commonly used to enhance user experience. Among these, Vitamin E acetate (VEA) was initially thought to be harmless but has been implicated as the primary cause of e-cigarette or vaping product use-associated lung injury, a serious lung disease. In our study, VEA serves as a proxy for other e-cigarette additives. To explore its harmful effects, we developed an exposure system to subject a pulmonary surfactant (PSurf) model to VEA-rich vapor. Through detailed analysis and atomic-level simulations, we found that VEA tends to cluster into aggregates on the PSurf surface, inducing deformations and weakening its essential elastic properties, critical for respiratory cycle function. Apart from VEA, our experiments also indicate that propylene glycol and vegetable glycerin, widely used in e-liquid mixtures, or their thermal decomposition products, alter surfactant properties. This research provides molecular-level insights into the detrimental impacts of vaping product additives on lung health.

• Klíčová slova
• EVALI, Lung surfactant, Molecular dynamics simulation, Pulmonary surfactant, Vaping-associated pulmonary injury,
• MeSH
• acetáty analýza   chemie   MeSH
• biologické modely MeSH
• lidé MeSH
• plicní surfaktanty * chemie   MeSH
• propylenglykol chemie   MeSH
• systémy dodávající nikotin elektronicky * MeSH
• vaping * škodlivé účinky   MeSH
• vitamin E * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetáty MeSH
• plicní surfaktanty * MeSH
• propylenglykol MeSH
• vitamin E * MeSH

This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.

• Klíčová slova
• exogenous surfactant, lung contusion, pulmonary contusion, pulmonary surfactant, surface‐active agents,
• MeSH
• bronchoskopie metody   MeSH
• lidé MeSH
• plicní surfaktanty * aplikace a dávkování   terapeutické užití   MeSH
• poškození plic * farmakoterapie   etiologie   MeSH
• syndrom dechové tísně * farmakoterapie   etiologie   MeSH
• umělé dýchání metody   MeSH
• výsledek terapie MeSH
• zhmoždění * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• plicní surfaktanty * MeSH

AIM: Minimally aggressive and easily performed techniques that facilitate spontaneous respiratory stabilisation are required to reduce rescue intubation in extremely premature infants. This study evaluated the feasibility and safety of administering surfactant into the pharynx of infants born at <25 weeks immediately after birth. METHODS: This study of 19 infants was conducted from January 2013 to June 2014 in a tertiary perinatal centre in Prague. We administered 1.5 mL of Curosurf as a bolus into the pharynx and simultaneously performed a sustained inflation manoeuvre (SIM). The extent of the interventions, death and severe neonatal morbidity in the study group were compared with 20 controls born before the study period and 20 born after it. RESULTS: All infants received oropharyngeal surfactant within the median (interquartile range) time of 40 seconds (25-75) after cord camping. The surfactant had to be suctioned in one infant because of upper airway obstruction. Although more subsequent surfactant was administered in the study group, significantly fewer study period infants required intubation than the before and after controls (16% versus 75% and 58%, respectively, p < 0.01). CONCLUSION: Oropharyngeal surfactant with simultaneous SIM was feasible and safe and reduced the need for delivery room intubation in these fragile infants.

• Klíčová slova
• Delivery room intubation, Oropharyngeal surfactant, Rescue intratracheal intubation, Threshold of viability,
• MeSH
• biologické přípravky aplikace a dávkování   MeSH
• fosfolipidy aplikace a dávkování   MeSH
• intratracheální intubace statistika a číselné údaje   MeSH
• lidé MeSH
• novorozenci extrémně nezralí MeSH
• novorozenec MeSH
• plicní surfaktanty aplikace a dávkování   MeSH
• resuscitace metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• Názvy látek
• biologické přípravky MeSH
• fosfolipidy MeSH
• plicní surfaktanty MeSH
• poractant alfa MeSH Prohlížeč

Lysosome-associated membrane glycoprotein 3 (LAMP3) is a type I transmembrane protein of the LAMP protein family with a cell-type-specific expression in alveolar type II cells in mice and hitherto unknown function. In type II pneumocytes, LAMP3 is localized in lamellar bodies, secretory organelles releasing pulmonary surfactant into the extracellular space to lower surface tension at the air/liquid interface. The physiological function of LAMP3, however, remains enigmatic. We generated Lamp3 knockout mice by CRISPR/Cas9. LAMP3 deficient mice are viable with an average life span and display regular lung function under basal conditions. The levels of a major hydrophobic protein component of pulmonary surfactant, SP-C, are strongly increased in the lung of Lamp3 knockout mice, and the lipid composition of the bronchoalveolar lavage shows mild but significant changes, resulting in alterations in surfactant functionality. In ovalbumin-induced experimental allergic asthma, the changes in lipid composition are aggravated, and LAMP3-deficient mice exert an increased airway resistance. Our data suggest a critical role of LAMP3 in the regulation of pulmonary surfactant homeostasis and normal lung function.

• MeSH
• bronchiální astma chemicky indukované   genetika   metabolismus   patologie   MeSH
• bronchoalveolární lavážní tekutina MeSH
• editace genu metody   MeSH
• homeostáza genetika   MeSH
• lipidomika MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• ovalbumin aplikace a dávkování   MeSH
• plíce metabolismus   patologie   MeSH
• plicní alveoly metabolismus   patologie   MeSH
• plicní surfaktanty metabolismus   MeSH
• pneumocyty metabolismus   patologie   MeSH
• protein - isoformy genetika   metabolismus   MeSH
• protein C asociovaný s plicním surfaktantem genetika   metabolismus   MeSH
• protein DC-LAMP nedostatek   genetika   MeSH
• regulace genové exprese MeSH
• respirační funkční testy MeSH
• rezistence dýchacích cest MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ovalbumin MeSH
• plicní surfaktanty MeSH
• protein - isoformy MeSH
• protein C asociovaný s plicním surfaktantem MeSH
• protein DC-LAMP MeSH
• Sftpc protein, mouse MeSH Prohlížeč

Over the past decade, there has been a significant rise in the use of vaping devices, particularly among adolescents, raising concerns for effects on respiratory health. Pressingly, many recent vaping-related lung injuries are unexplained by current knowledge, and the overall implications of vaping for respiratory health are poorly understood. This study investigates the effect of hydrophobic vaping liquid chemicals on the pulmonary surfactant biophysical function. We focus on the commonly used flavoring benzaldehyde and its vaping byproduct, benzaldehyde propylene glycol acetal. The study involves rigorous testing of the surfactant biophysical function in Langmuir trough and constrained sessile drop surfactometer experiments with both protein-free synthetic surfactant and hydrophobic protein-containing clinical surfactant models. The study reveals that exposure to these vaping chemicals significantly interferes with the synthetic and clinical surfactant biophysical function. Further atomistic simulations reveal preferential interactions with SP-B and SP-C surfactant proteins. Additionally, data show surfactant lipid-vaping chemical interactions and suggest significant transfer of vaping chemicals to the experimental subphase, indicating a toxicological mechanism for the alveolar epithelium. Our study, therefore, reveals novel mechanisms for the inhalational toxicity of vaping. This highlights the need to reassess the safety of vaping liquids for respiratory health, particularly the use of aldehyde chemicals as vaping flavorings.

• Klíčová slova
• e-cigarettes, exposure and human health, inhalation toxicology, lung surfactant, mechanistic toxicology, vaping,
• MeSH
• aldehydy MeSH
• benzaldehydy MeSH
• chuťové esence MeSH
• lidé MeSH
• mladiství MeSH
• plicní surfaktanty * MeSH
• povrchově aktivní látky MeSH
• systémy dodávající nikotin elektronicky * MeSH
• vaping * MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aldehydy MeSH
• benzaldehydy MeSH
• chuťové esence MeSH
• plicní surfaktanty * MeSH
• povrchově aktivní látky MeSH

The study was designed to prove the hypothesis that lipopolysaccharide (LPS)-induced fever elicits the changes in surfactant specific proteins, potentially related to thermal tachypnea. In adult rats fever was induced by intraperitoneal administration of LPS at a dose 100 microg/kg of body weight; control group received saline. Respiratory parameters, arterial blood gases and pH and colonic body temperature (BT) were recorded. Five hours later, surfactant proteins (SP) A, B, C and D were evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue (LT). LPS evoked monophasic thermic response (at 300 min 38.7+/-0.2 vs. 36.4+/-0.3 °C, P 0.05) and an increase in minute ventilation due to changes in breathing rate and tidal volume. LPS-instilled animals had higher levels of SP-A and SP-D in LT (P 0.05 and 0.01), and higher SP-D in BALF (P 0.01) than controls. SP-B increased in LT and SP-C in BALF of animals with LPS (both P 0.05 vs. controls). The changes in all surfactant specific proteins are present in LPS-induced fever. Alterations of proteins related to local immune mechanisms (SP-A, SP-D) are probably a part of general inflammatory response to pyrogen. Changes in proteins related to surface activity (SP-B and SP-C) might reflect the effort of the body to stabilize the lungs in thermal challenge.

• MeSH
• aldosteron krev   MeSH
• bronchoalveolární lavážní tekutina chemie   MeSH
• dýchání * MeSH
• horečka metabolismus   patofyziologie   MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• lipopolysacharidy MeSH
• náhodné rozdělení MeSH
• počet leukocytů MeSH
• potkani Wistar MeSH
• proteiny asociované s plicním surfaktantem analýza   metabolismus   MeSH
• tělesná teplota MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldosteron MeSH
• látky reagující s kyselinou thiobarbiturovou MeSH
• lipopolysacharidy MeSH
• proteiny asociované s plicním surfaktantem MeSH