Pulmonary Surfactant System Research Articles

Albumin Proteins as Delivery Vehicles for PFAS Contaminants into Respiratory Membranes.

Poly- and perfluoroalkyl substances (PFAS) are a family of chemicals that have been used in a wide range of commercial products. While their use is declining, the prevalence of PFAS, combined with their chemical longevity, ensures that detectable levels will remain in the environment for years to come. As such, there is a pressing need to understand how PFAS contaminants interact with other elements of the human exposome and the consequences of these interactions for human health. Using serum albumin as a model system, we show that proteins can bind PFAS contaminants and facilitate their incorporation into model pulmonary surfactant systems and lipid bilayers. Protein-mediated PFAS delivery significantly altered the structure and function of both model membrane systems, potentially contributing to respiratory dysfunction and airway diseases in vivo. These results provide valuable insights into the synergistic interaction between PFAS contaminants and other elements of the human exposome and their potential consequences for human health.

Biochemical criteria for pulmonary surfactant damage in tuberculosis patients with previous work in dusty conditions

Introduction. Among the mechanisms of pathogenesis of tuberculosis is damage to the pulmonary surfactant. In patients with tuberculosis who previously worked in an industrial dusty environment, the pulmonary surfactant system is affected by two damaging factors simultaneously.The aim of the work was to determine the role of biochemical criteria of pulmonary surfactant damage as early molecular markers of the sub-radiological stage of pneumoconiosis in pulmonary tuberculosis patients.Materials and methods. The object of the study was 91 patients with pulmonary tuberculosis, of whom 59 patients had contact with industrial quartz-containing dust in the course of their work (the main group) and 32 patients − with an unburdened professional route (the control group). The content of total protein (TP), total phospholipids (TPL), phospholipid spectrum by thin-layer chromatography as criteria of pulmonary surfactant damage were studied biochemically in bronchoalveolar flushes (BAF).Results. It was found that in bronchoalveolar flushes of patients with tuberculosis of dust-hazardous professions, in group 1, the content of total protein increases, while the level of total phospholipids does not statistically significantly change in comparison with patients with an unburdened professional route. Among the phospholipids of BAF, phosphatidylcholine (PC), phosphatidiylethanolamine (PEA) and cardiolipin (CL) are the most common. In the BAF of the 1st group of patients, a frequent combination of fractions of PC and CL was found, in the 2nd group − PC, PEA and CL. Combinations containing sphingomyelin (SPM), PC and CL were found only in groups 1 and 2. It was also found that the level of total protein in BAF varies depending on the activity of the process, so in patients of group 1 with the presence of areas of destruction of lung tissue, the content of total protein significantly exceeded that in patients with specific inflammation subsiding.Discussion. Patients with pulmonary tuberculosis with dust exposure develop sub-radiological manifestations of pneumoconiosis in the form of impaired metabolism and biochemical composition of pulmonary surfactant, which is caused both by the dust factor and the influence of specific inflammation.Conclusion The role of biochemical criteria of pulmonary surfactant damage as early molecular markers of the sub-radiological stage of pneumoconiosis in pulmonary tuberculosis patients was determined.

The anti-inflammatory and antiviral properties of anionic pulmonary surfactant phospholipids.

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.

Surfactant dysfunction due to e-cigarette aerosol exposure with and without additional insults

Introduction: The use of e-cigarettes (ECs) remains a popular habit for young populations, in part due to the variety of appealing flavours available. However, EC use has been associated with acute lung injury via unknown mechanisms. During a deep inhalation, one of the first compounds the EC aerosol comes into contact within the lungs is pulmonary surfactant. This complex mixture of lipids and surfactant associated proteins lines the alveolar surface and reduces surface tension to near zero values upon exhalation. Surfactant dysfunction, associated with serum protein leak and oxidative stress, contributes to lung injury. We hypothesized that exposure to EC aerosol impairs pulmonary surfactant function, and thereby increases its susceptibility to protein inhibition or oxidative stress. Methods: Bovine lipid extract surfactant (BLES) was used as a model exogenous surfactant. 2ml of BLES (2mg/ml) was placed in a syringe (30ml) attached to an EC, drawing in and expelling the aerosol 30 times. Vehicle e-liquid (VG:PG 50:50) as well as e-liquid containing flavouring additives and nicotine were utilized. Two models of injury were used, the first being addition of serum containing plasma proteins and the second oxidization by hypochlorous acid following aerosol exposure. Surface tension reduction of all samples after exposure was performed using a constrained drop surfactometer (CDS), where samples underwent 20 dynamic compression and expansion cycles. Results: Minimum surfaces tensions were significantly higher after exposure to EC aerosol across 20 compression/expansion cycles. Menthol and red wedding flavoured aerosol exposure resulted in significantly increased minimum surface tensions compared to unflavoured vehicle e-liquid, although nicotine had no additional effects beyond that of the vehicle e-liquid. The addition of plasma containing serum proteins significantly increased minimum surface tensions in aerosol exposed samples compared to those unexposed to serum and air controls. Oxidized surfactant had higher minimum surface tensions compared to control, however EC aerosol exposure had no additional effect on the inhibition of the surfactant’s function. Conclusion: EC aerosols alter surfactant function through increases in minimum surface tension. Variability in the severity of inhibition exists between flavouring additives, however the base common across all e-liquids is able to effectively inhibit surfactant. This inhibition is amplified in the presence of serum proteins. From these results we conclude that vaping impairs the pulmonary surfactant system and increases susceptibility to damage by secondary insults. Lawson Health Research Institute, NSERC This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Эволюция представлений о системе легочного сурфактанта

Эволюция представлений о системе легочного сурфактанта

Elucidating the enhanced binding affinity of a double mutant SP-D with trimannose on the influenza A virus using molecular dynamics

Surfactant protein D (SP-D) is an essential component of the human pulmonary surfactant system, which is crucial in the innate immune response against glycan-containing pathogens, including Influenza A viruses (IAV) and SARS-CoV-2. Previous studies have shown that wild-type (WT) SP-D can bind IAV but exhibits poor antiviral activities. However, a double mutant (DM) SP-D consisting of two point mutations (Asp325Ala and Arg343Val) inhibits IAV more potently. Presently, the structural mechanisms behind the point mutations’ effects on SP-D’s binding affinity with viral surface glycans are not fully understood. Here we use microsecond-scale, full-atomistic molecular dynamics (MD) simulations to understand the molecular mechanism of mutation-induced SP-D’s higher antiviral activity. We find that the Asp325Ala mutation promotes a trimannose conformational change to a more stable state. Arg343Val increases the binding with trimannose by increasing the hydrogen bonding interaction with Glu333. Free energy perturbation (FEP) binding free energy calculations indicate that the Arg343Val mutation contributes more to the increase of SP-D’s binding affinity with trimannose than Asp325Ala. This study provides a molecular-level exploration of how the two mutations increase SP-D binding affinity with trimannose, which is vital for further developing preventative strategies for related diseases.

Development and functional significance of the pulmonary surfactant system

Relevance. Prevention of the development of postoperative acute respiratory distress syndrome during operations on the descending thoracic aorta increases the effectiveness of therapy. The study of damage to the surfactant complex during ischemia and reperfusion of the lungs is relevant, since it involves the prophylactic use of the surfactant preparation during operations on the descending part of the thoracic aorta, which are characterized by a high risk of postoperative acute respiratory distress syndrome. Objective: to increase the effectiveness of pharmacological and respiratory therapy of acute respiratory distress syndrome, as well as to identify the role of the surfactant system of the lungs in the onset of inflammation against the background of tuberculosis and the development of regeneration mechanisms that affect the course and outcome of the disease. Materials and Methods. The study involved 24 people, including 14 volunteer patients with a diagnosed respiratory disease in an acute course (while the whole group received the drug from the study as an additional therapy). The sample of 14 people was formed solely due to the compliance of these patients with the criteria that were established before the start of the study of the drug, which had postoperative acute respiratory distress syndrome of various origins in their diagnosis. Results and Discussion. For a comprehensive laboratory determination, an algorithm was used that corresponded to the state standard to identify postoperative acute respiratory distress syndrome. For each participant in the experiments, it was proposed to develop a plan of treatment procedures, taking into account individualization and standardization. Conclusion. Some of the resulting data are collected with respect to the surfactant pulmonary system, which is presented in a compactor model format. A number of basic components are reflected here, which are classified according to cellular and non-cellular factors. At the same time, the surfactant substance helps to reduce the pronounced swelling, which can significantly reduce the process of sticking of the alveolar structures during inhalation. All this added up to the normal system of gas metabolism in the lung structures, including the control of the mucociliary system, which acts as a natural stimulator of the function of alveolar macrophages.

Sirtuin 3 Ameliorates Lung Senescence and Improves Type II Alveolar Epithelial Cell Function by Enhancing the FoxO3a-Dependent Antioxidant Defense Mechanism.

Lung aging alters the intrinsic structure of the lung and pulmonary surfactant system and increases the mortality and morbidity due to respiratory diseases in elderly individuals. We hypothesized that lung aging results from an insufficiency of type II alveolar epithelial cells (AECIIs) in the lung tissue. Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased SIRT3 expression has been linked to an extended life span in humans. Hence, we speculated that the overexpression of SIRT3 may help to ameliorate lung senescence and improve AECII function. AECIIs were isolated from young and old patients with pneumothorax caused by pulmonary bullae. The expression of SIRT3, manganese superoxide dismutase, and catalase, as well as cell function and senescence indicators of young and old AECIIs, was measured before and after SIRT3 overexpression. After SIRT3 overexpression, the aged state of old AECIIs improved, and antiapoptotic activity, proliferation, and secretion were dramatically enhanced. Surfactant protein C (SPC), which is secreted by AECIIs, reduces alveolar surface tension, repairs the alveolar structure, and regulates inflammation. SPC deficiency in patients is associated with increased inflammation and delayed repair. SIRT3 deacetylated forkhead box O3a, thereby protecting mitochondria from oxidative stress and improving cell function and the senescent state of old AECIIs. These findings provide a possible direction for aging-delaying therapies and interventions for diseases of the respiratory system.

Simulated Breathing: Application of Molecular Dynamics Simulations to Pulmonary Lung Surfactant

In this review, we delve into the topic of the pulmonary surfactant (PS) system, which is present in the respiratory system. The total composition of the PS has been presented and explored, from the types of cells involved in its synthesis and secretion, down to the specific building blocks used, such as the various lipid and protein components. The lipid and protein composition varies across species and between individuals, but ultimately produces a PS monolayer with the same role. As such, the composition has been investigated for the ways in which it imposes function and confers peculiar biophysical characteristics to the system as a whole. Moreover, a couple of theories/models that are associated with the functions of PS have been addressed. Finally, molecular dynamic (MD) simulations of pulmonary surfactant have been emphasized to not only showcase various group’s findings, but also to demonstrate the validity and importance that MD simulations can have in future research exploring the PS monolayer system.

Role of pulmonary surfactant protein Sp-C dimerization on membrane fragmentation: An emergent mechanism involved in lung defense and homeostasis

Surfactant protein C (SP-C) is a protein present in the pulmonary surfactant system that is involved in the biophysical properties of this lipoprotein complex, but it also has a role in lung defense and homeostasis. In this article, we propose that the link between both functions could rely on the ability of SP-C to induce fragmentation of phospholipid membranes and generate small vesicles that serve as support to present different ligands to cells in the lungs. Our results using bimolecular fluorescence complementation and tunable resistive pulse sensing setups suggest that SP-C oligomerization could be the triggering event that causes membrane budding and nanovesiculation. As shown by fluorescence microscopy and flow cytometry, these vesicles are differentially assimilated by alveolar macrophages and alveolar type II cells, indicating distinct roles of these alveoli-resident cells in the processing of the SP-C- induced vesicles and their cargo. These results depict a more accurate picture of the mechanisms of this protein, which could be relevant for the comprehension of pulmonary pathologies and the development of new therapeutic approaches.

Interfacial Delivery of Surfactant Protein SP-D through its Association with Pulmonary Surfactant

Surfactant protein D (SP-D) is a glycoprotein part of the pulmonary surfactant (PS) system that carries out important roles in the innate immune defense of the lungs and participates in surfactant homeostasis. Pulmonary surfactant (PS) is a lipid-protein complex, synthesized and secreted to the alveolar space by type II pneumocytes. It spontaneously adsorbs and spreads over the air-liquid interface, reducing the surface tension and enabling the process of breathing. PS has been recently proposed as a drug delivery carrier due to its unique surface-active properties and its peculiar composition.

Pulmonary Surfactant and Drug Delivery: An Interface-Assisted Carrier to Deliver Surfactant Protein SP-D Into the Airways

This work is focused on the potential use of pulmonary surfactant to deliver full-length recombinant human surfactant protein SP-D (rhSP-D) using the respiratory air-liquid interface as a shuttle. Surfactant protein D (SP-D) is a collectin protein present in the pulmonary surfactant (PS) system, involved in innate immune defense and surfactant homeostasis. It has been recently suggested as a potential therapeutic to alleviate inflammatory responses and lung diseases in preterm infants suffering from respiratory distress syndrome (RDS) or bronchopulmonary dysplasia (BPD). However, none of the current clinical surfactants used for surfactant replacement therapy (SRT) to treat RDS contain SP-D. The interaction of SP-D with surfactant components, the potential of PS as a respiratory drug delivery system and the possibility to produce recombinant versions of human SP-D, brings the possibility of delivering clinical surfactants supplemented with SP-D. Here, we used an in vitro setup that somehow emulates the respiratory air-liquid interface to explore this novel approach. It consists in two different compartments connected with a hydrated paper bridge forming a continuous interface. We firstly analyzed the adsorption and spreading of rhSP-D alone from one compartment to another over the air-liquid interface, observing low interfacial activity. Then, we studied the interfacial spreading of the protein co-administered with PS, both at different time periods or as a mixed formulation, and which oligomeric forms of rhSP-D better traveled associated with PS. The results presented here demonstrated that PS may transport rhSP-D long distances over air-liquid interfaces, either as a mixed formulation or separately in a close window time, opening the doors to empower the current clinical surfactants and SRT.

Evaluation of Regional Pulmonary Ventilation in Spontaneously Breathing Patients with Idiopathic Pulmonary Fibrosis (IPF) Employing Electrical Impedance Tomography (EIT): A Pilot Study from the European IPF Registry (eurIPFreg).

Objectives: In idiopathic pulmonary fibrosis (IPF), alterations in the pulmonary surfactant system result in an increased alveolar surface tension and favor repetitive alveolar collapse. This study aimed to assess the usefulness of electrical impedance tomography (EIT) in characterization of regional ventilation in IPF. Materials and methods: We investigated 17 patients with IPF and 15 healthy controls from the University of Giessen and Marburg Lung Center (UGMLC), Germany, for differences in the following EIT parameters: distribution of ventilation (TID), global inhomogeneity index (GI), regional impedance differences through the delta of end-expiratory lung impedance (dEELI), differences in surface of ventilated area (SURF), as well as center of ventilation (CG) and intratidal gas distribution (ITV). These parameters were assessed under spontaneous breathing and following a predefined escalation protocol of the positive end-expiratory pressure (PEEP), applied through a face mask by an intensive care respirator (EVITA, Draeger, Germany). Results: Individual slopes of dEELI over the PEEP increment protocol were found to be highly significantly increased in both groups (p < 0.001) but were not found to be significantly different between groups. Similarly, dTID slopes were increasing in response to PEEP, but this did not reach statistical significance within or between groups. Individual breathing patterns were very heterogeneous. There were no relevant differences of SURF, GI or CGVD over the PEEP escalation range. A correlation of dEELI to FVC, BMI, age, or weight did not forward significant results. Conclusions: In this study, we did see a significant increase in dEELI and a non-significant increase in dTID in IPF patients as well as in healthy controls in response to an increase of PEEP under spontaneous breathing. We propose the combined measurements of EIT and lung function to assess regional lung ventilation in spontaneously breathing subjects.

EXOGENOUS SURFACTANTS OF NATURAL ORIGIN IN THE TREATMENT OF RESPIRATORY DISTRESS SYNDROME - COMPARATIVE COMPOSITION, BIOPHYSICAL PROPERTIES AND CLINICAL EFFECTIVENESS

Respiratory distress syndrome (RDS) remains an important cause of morbidity and mortality in premature infants in Ukraine and around the world. Since the determination of surfactant deficiency as the main cause of this disease, significant progress has been made in studying the structure and function of the pulmonary surfactant system, as well as the possibilities of creating and effective use of exogenous surfactant preparations. Unprecedented long-term fundamental, experimental and clinical studies have ensured the clinical availability of numerous exogenous surfactant preparations, the use of which is currently considered one of the standards of neonatal care, regardless of the level of development of the country. However, all these surfactants are not alike. Although all surfactants licensed for clinical practice significantly reduce mortality in preterm infants from RDS, they differ in phospholipid and protein composition, phospholipid concentration, biophysical properties, dosage, possibilities of less invasive administration, applicability, and clinical efficacy. Comparative clinical studies have shown the benefits of poractant-α, which can be administered at a dose that provides more phospholipids in a smaller volume, contains more surfactant-specific proteins (primarily SPB), and is licensed for administration by the less invasive method. The developers of third-generation synthetic surfactants, which have already demonstrated their clinical effectiveness, place their main hopes on the imitation of these properties. This review presents current data on the structure, composition, and biophysical properties of pulmonary surfactant, provides a comparative description of the most commonly used preparations of exogenous surfactant of animal origin, and characterizes additional prerequisites for the effective use of surfactant therapy.

Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis

Pulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface.

Protective effects of aerosolized pulmonary surfactant powder in a model of ventilator-induced lung injury.

Mechanical ventilation may contribute to the impairment of the pulmonary surfactant system, which is one of the mechanisms leading to the progression of acute lung injury. To investigate the potential protective effects of pulmonary surfactant in a rat model of ventilator-induced lung injury, the surfactant powder was aerosolized using an in-house made device designed to deliver the aerosolized powder to the inspiratory line of a rodent ventilator circuit. Rats were randomized to (i) administration of aerosolized recombinant surfactant protein C based pulmonary surfactant, (ii) intratracheally instillation of the same surfactant re-constituted in saline, and (iii) no treatment. Animals were monitored during 2h of high-tidal volume mechanical ventilation, after which rats were sacrificed, and further analysis of lung mechanics and surfactant function were completed. Blood gas measurements during ventilation showed extended maintenance of oxygen levels above 400mmHg in aerosol treated animals over non-treated and instilled groups, while total protein analysis showed reduced levels in the aerosol compared to non-treated groups. Dynamic captive bubble surface tension measurements showed the activity of surfactant recovered from aerosol treated animals is maintained below 1 mN/m. The prophylactic treatment of aerosolized surfactant powder reduced the severity of lung injury in this model.

STUDY OF ACTIVATING EFFECT OF SURFACTANT DRUGS ON PULMONARY MACROPHAGES IN VITRO IN PATIENTS WITH BRONCHIECTASIS

The state of surfactant system of lungs in chronic inflammation is known to disrupt their structural organization, causes shifts in the system itself, the severity of which depends on alveolar parenchyma injury rate. The cell destruction of aerohematical barrier is accompanied by changes in pulmonary surfactant system, its deficiency, development of dis− and atelectases, which increases the severity of lung injury and promotes the progression of bronchiectasis. Exogenously introduced surfactant restores local immunity and serves as a substrate for synthesis of its own surfactant. To determine the stimulatory effect of natural surfactant on receptors of the lung macrophages and its influence on activation of phagocytosis a comparative study of direct effect of infasurf on cell surface and formation of phagocytic vacuoles in macrophage elements of individuals with bronchodectic disease at an acute stage was performed . In bronchoalveolar lavage of patients the percentage and viability of pulmonary macrophages were determined. Other lavage material was investigated both as a baseline control and with infasurf. The electron microscopic examination of bronchoalveolar lavage macrophage elements in patients show that after incubation of cells with infasurf, there is a pronounced cell surface activation, formation of phagocytic vacuoles containing membranes of exogenous surfactant. Its small and large clusters were often observed lying freely between pulmonary macrophages, whereas in the control group (without infasurf) small fragments of tubular myelin or osmiophilous lamellar bodies were noted. Thus, the specific pharmacological action of surfactant drugs directly contributes to differentiation and maturation of pulmonary macrophages, their phagocytic function activation. Key words: bronchiectasis, surfactant, pulmonary macrophages.

Native supramolecular protein complexes in pulmonary surfactant: Evidences for SP-A/SP-B interactions

Pulmonary surfactant is a lipid-protein complex which coats lung alveoli. It displays the essential function of reducing surface tension at the air-liquid interface, avoiding alveolar collapse during expiration. The optimized biophysical properties of surfactant rely on its defined composition, constituted mainly by phospholipids and tiny amounts of lipid-associated specific proteins. Due to the highly hydrophobic nature of surfactant, organic solvents have been traditionally employed to obtain and characterize surfactant lipids and proteins, very likely leading to disruption of native interactions among its components. In the present work we have addressed the search of native protein complexes in pulmonary surfactant, which could have an essential role in the optimal function of the system. By solubilizing native lipid-protein membranes of surfactant with non-denaturing detergents, and with the use of a two-dimensional electrophoresis strategy, we have been able to detect the presence of supramolecular complexes composed of surfactant proteins SP-A, SP-B and SP-C. Furthermore, by co-immunoprecipitation assays, we have confirmed for the first time the existence of a direct interaction between SP-A and SP-B, an important feature which could explain the known functional cooperation of both proteins in several aspects of surfactant biology. SignificanceThis paper deepens for the first time in the existence of complex interaction networks of surfactant proteins in native surfactant membranes. By the use of non-denaturing detergents, two-dimensional electrophoresis and immunoprecipitation, we have been able to make progress in the elucidation of native protein complexes in this essential system, that had been previously hindered by the classical purification protocols employing organic solvents. In this work, we have described the presence of interactions between SP-B and SP-A, two important proteins whose functional cooperation has been broadly reported in the literature. Pioneer determination of such native complexes could have potential implications for understanding the wide variety of roles of pulmonary surfactant system.

The effects of aging and exercise on lung mechanics, surfactant and alveolar macrophages

Purpose: Advancing age leads to changes to the respiratory system associated with increased susceptibility to lung diseases, and exercise may counteract this effect. To explore the underlying processes, we investigated the effects of aging and exercise on lung mechanics, alveolar macrophage function, and surfactant pools and activity, in mice. It was hypothesized that aging would impact lung mechanics, macrophage polarization, and the status of the surfactant system, and that these changes would be mitigated by exercise. Methods: Male C57BL/6 mice were housed from 2-3 to 22 months, for the aged group, or until 4 months of age for young mice. Mice in both groups were randomized to voluntarily running exercise or to non-exercise, for a 2-month period. Mice were euthanized and lung mechanics were analyzed using a flexiVent ventilator. Subsequently, the lungs were lavaged to obtain pulmonary surfactant and alveolar macrophages. Pulmonary surfactant was analyzed for pool sizes and activity whereas alveolar macrophages were examined for response to pro and anti-inflammatory stimuli. Results: Changes in lung mechanics, such as increased compliance and decreased airway resistance, were associated with aging but were not affected by exercise. The quantity as well as the biophysical activity of the pulmonary surfactant system was unaffected by either aging or exercise. More alveolar macrophages were recovered from exercising aged mice compared to both the young and non-exercising groups. Macrophages in this aged exercise group were more responsive to an anti-inflammatory stimulus. Conclusions: Our data supports previous literature that suggest the development of emphysema-like alterations to lung mechanics with aging. This effect was independent of exercise. Our data also indicates that surfactant is unaffected by aging and exercise. Alveolar macrophage properties and numbers were affected by exercise in the aging lung and may represent the main, potentially beneficial, effect of exercise on the pulmonary system.

The effects of aging and exercise on lung mechanics, surfactant and alveolar macrophages

IntroductionIt has been well established that advancing age leads to changes to the respiratory system and an associated susceptibility to lung diseases. Furthermore, exercise may counteract this pulmonary disease susceptibility. To start to investigate the underlying processes of these effects we explored the baseline characteristics due to aging and exercise on lung mechanics and on two important components of a healthy pulmonary environment, alveolar macrophage function and the pulmonary surfactant system. It was hypothesized that aging would impact lung mechanics, macrophage polarization and the status of the surfactant system, and that these changes would be mitigated by exercise.Experimental approach: Male C57BL/6 mice were housed from 2–3 to 22 months, for the aged group, or until 4 months of age for young control mice. Mice in both the young and aged groups were randomized to either voluntarily running exercise or non‐exercise for a 2 month period. Mice were euthanized and lung mechanics were analyzed using a Flexivent ventilator. Subsequently, the lungs were lavaged to obtain pulmonary surfactant and alveolar macrophages. Pulmonary surfactant was analyzed for surfactant pool sizes and activity whereas alveolar macrophages were examined for a response to pro‐and anti‐inflammatory stimuli.ResultsChanges in lung mechanics, such as increased compliance and decreased airway resistance, were observed in the aged cohorts. These changes were not affected by exercise.The quantity as well as the biophysical activity of the pulmonary surfactant system was unaffected by either aging or exercise. More alveolar macrophages were recovered from exercising aged mice as compared to both the young and non‐exercising groups.Support or Funding InformationWestern Strategic Support, Lawson Internal Research FundsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.