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Thorax Aug 2005
Topics: Animals; DNA; Drug Interactions; Drug Therapy, Combination; Humans; Models, Animal; Pneumonia; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Protein D; Pulmonary Surfactants
PubMed: 16061700
DOI: 10.1136/thx.2004.036699 -
Therapeutic Delivery Aug 2013Lung surfactant is crucial for optimal pulmonary function throughout life. An absence or deficiency of surfactant can affect the surfactant pool leading to respiratory... (Review)
Review
Lung surfactant is crucial for optimal pulmonary function throughout life. An absence or deficiency of surfactant can affect the surfactant pool leading to respiratory distress. Even if the coupling between surfactant dysfunction and the underlying disease is not always well understood, using exogenous surfactants as replacement is usually a standard therapeutic option in respiratory distress. Exogenous surfactants have been extensively studied in animal models and clinical trials. The present article provides an update on the evolution of surfactant therapy, types of surfactant treatment, and development of newer-generation surfactants. The differences in the performance between various surfactants are highlighted and advanced research that has been conducted so far in developing the optimal delivery of surfactant is discussed.
Topics: Aerosols; Animals; Drug Delivery Systems; Humans; Laryngeal Masks; Lung Diseases; Nebulizers and Vaporizers; Pulmonary Surfactants
PubMed: 23919474
DOI: 10.4155/tde.13.72 -
Frontiers in Immunology 2022
Topics: Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Immunity, Innate; Surface-Active Agents
PubMed: 36582248
DOI: 10.3389/fimmu.2022.1113210 -
Annals of the American Thoracic Society May 2015Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with... (Review)
Review
Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension-lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications.
Topics: Humans; Lung Diseases; Pulmonary Surfactants; Respiratory Tract Infections
PubMed: 25742123
DOI: 10.1513/AnnalsATS.201411-507FR -
European Journal of Pharmaceutics and... Nov 2022This work evaluates interaction of pulmonary surfactant (PS) and antimicrobial peptides (AMPs) in order to investigate (i) if PS can be used to transport AMPs, and (ii)...
This work evaluates interaction of pulmonary surfactant (PS) and antimicrobial peptides (AMPs) in order to investigate (i) if PS can be used to transport AMPs, and (ii) to what extent PS interferes with AMP function and vice versa. This, in turn, is motivated by a need to find new strategies to treat bacterial infections in the airways. Low respiratory tract infections (LRTIs) are a leading cause of illness and death worldwide that, together with the problem of multidrug-resistant (MDR) bacteria, bring to light the necessity of developing effective therapies that ensure high bioavailability of the drug at the site of infection and display a potent antimicrobial effect. Here, we propose the combination of AMPs with PS to improve their delivery, exemplified for the hydrophobically end-tagged AMP, GRR10W4 (GRRPRPRPRPWWWW-NH), with previously demonstrated potent antimicrobial activity against a broad spectrum of bacteria under various conditions. Experiments using model systems emulating the respiratory interface and an operating alveolus, based on surface balances and bubble surfactometry, served to demonstrate that a fluorescently labelled version of GRR10W4 (GRR10W4-F), was able to interact and insert into PS membranes without affecting its biophysical function. Therefore, vehiculization of the peptide along air-liquid interfaces was enabled, even for interfaces previously occupied by surfactants layers. Furthermore, breathing-like compression-expansion dynamics promoted the interfacial release of GRR10W4-F after its delivery, which could further allow the peptide to perform its antimicrobial function. PS/GRR10W4-F formulations displayed greater antimicrobial effects and reduced toxicity on cultured airway epithelial cells compared to that of the peptide alone. Taken together, these results open the door to the development of novel delivery strategies for AMPs in order to increase the bioavailability of these molecules at the infection site via inhaled therapies.
Topics: Pulmonary Surfactants; Tryptophan; Antimicrobial Peptides; Anti-Infective Agents; Anti-Bacterial Agents; Adenosine Monophosphate; Microbial Sensitivity Tests
PubMed: 36154903
DOI: 10.1016/j.ejpb.2022.09.018 -
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 -
Current Medicinal Chemistry 2008Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant... (Review)
Review
Pulmonary surfactant is a lipid-protein complex that coats the interior of the alveoli and enables the lungs to function properly. Upon its synthesis, lung surfactant adsorbs at the interface between the air and the hypophase, a capillary aqueous layer covering the alveoli. By lowering and modulating surface tension during breathing, lung surfactant reduces respiratory work of expansion, and stabilises alveoli against collapse during expiration. Pulmonary surfactant deficiency, or dysfunction, contributes to several respiratory pathologies, such as infant respiratory distress syndrome (IRDS) in premature neonates, and acute respiratory distress syndrome (ARDS) in children and adults. The main clinical exogenous surfactants currently in use to treat some of these pathologies are essentially organic extracts obtained from animal lungs. Although very efficient, natural surfactants bear serious defects: i) they could vary in composition from batch to batch; ii) their production involves relatively high costs, and sources are limited; and iii) they carry a potential risk of transmission of animal infectious agents and the possibility of immunological reaction. All these caveats justify the necessity for a highly controlled synthetic material. In the present review the efforts aimed at new surfactant development, including the modification of existing exogenous surfactants by adding molecules that can enhance their activity, and the progress achieved in the production of completely new preparations, are discussed.
Topics: Amino Acid Sequence; Animals; Humans; Lipids; Models, Molecular; Molecular Sequence Data; Pulmonary Surfactants; Structure-Activity Relationship
PubMed: 18288994
DOI: 10.2174/092986708783497364 -
Langmuir : the ACS Journal of Surfaces... Mar 2023The 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...
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 -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.
Topics: Biophysical Phenomena; Phospholipids; Proteins; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactants; Surface Properties; Surface-Active Agents; Pulmonary Surfactant-Associated Protein C
PubMed: 36917773
DOI: 10.1021/acs.langmuir.2c03349 -
Biochimica Et Biophysica Acta 2008The pulmonary surfactant system constitutes an excellent example of how dynamic membrane polymorphism governs some biological functions through specific lipid-lipid,... (Review)
Review
The pulmonary surfactant system constitutes an excellent example of how dynamic membrane polymorphism governs some biological functions through specific lipid-lipid, lipid-protein and protein-protein interactions assembled in highly differentiated cells. Lipid-protein surfactant complexes are assembled in alveolar pneumocytes in the form of tightly packed membranes, which are stored in specialized organelles called lamellar bodies (LB). Upon secretion of LBs, surfactant develops a membrane-based network that covers rapidly and efficiently the whole respiratory surface. This membrane-based surface layer is organized in a way that permits efficient gas exchange while optimizing the encounter of many different molecules and cells at the epithelial surface, in a cross-talk essential to keep the whole organism safe from potential pathogenic invaders. The present review summarizes what is known about the structure of the different forms of surfactant, with special emphasis on current models of the molecular organization of surfactant membrane components. The architecture and the behaviour shown by surfactant structures in vivo are interpreted, to some extent, from the interactions and the properties exhibited by different surfactant models as they have been studied in vitro, particularly addressing the possible role played by surfactant proteins. However, the limitations in structural complexity and biophysical performance of surfactant preparations reconstituted in vitro will be highlighted in particular, to allow for a proper evaluation of the significance of the experimental model systems used so far to study structure-function relationships in surfactant, and to define future challenges in the design and production of more efficient clinical surfactants.
Topics: Animals; Biophysical Phenomena; Biophysics; Humans; Membrane Lipids; Membrane Proteins; Models, Biological; Models, Molecular; Molecular Structure; Myelin Sheath; Pulmonary Alveoli; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants
PubMed: 18515069
DOI: 10.1016/j.bbamem.2008.05.003 -
MEDICC Review Oct 2022In inflammatory respiratory diseases, the imbalance between proteases and endogenous protease inhibitors leads to an exacerbated activity of human neutrophil elastase (a...
INTRODUCTION
In inflammatory respiratory diseases, the imbalance between proteases and endogenous protease inhibitors leads to an exacerbated activity of human neutrophil elastase (a protease that destroys the extracellular matrix and stimulates proinflammatory cytokine release). Elastase is considered a target in the search for therapeutic treatments for inflammatory respiratory diseases. Pulmonary surfactant is a promising product for this purpose, because in addition to its biophysical function, it has anti-inflammatory properties.
OBJECTIVE
Evaluate effect of the Cuban porcine pulmonary surfactant (Surfacen), the rCmPI-II elastase inhibitor, and the Surfacen/rCmPI-II combination on activated neutrophil elastase activity in vitro, and determine if Surfacen's interface property changes in the presence of the inhibitor.
METHODS
The anti-elastase effect of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination was evaluated in an in vitro model of activated neutrophils, previously purified from the blood of healthy subjects. The cells were stimulated with LPS/fMLP and were incubated with different concentrations of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination. Elastase activity was measured. The interface property was determined on a Langmuir surface balance. The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor.
RESULTS
Surfacen at 10 mg/mL inhibited 71% of stimulated neutrophil elastase activity. rCmPI-II at 0.1 μM reduced 20% of elastase activity; at 200 μM-the maximum concentration evaluated-inhibition was 68%. Both products had a dose-dependent effect. The Surfacen/inhibitor combination (0.5 mg/mL/80 µM) did not affect the surfactant interface property or the inhibitory activity of rCmPI-II against human neutrophil elastase.
CONCLUSIONS
Surfacen and the rCmPI-II inhibitor have an anti-elastase effect on an activated neutrophil model. rCmPI-II does not affect Surfacen's interface property and, therefore, both can be evaluated for combined use in treating inflammatory lung diseases.
Topics: Animals; Humans; Antiviral Agents; Leukocyte Elastase; Neutrophils; Protease Inhibitors; Pulmonary Surfactants; Swine
PubMed: 36417334
DOI: 10.37757/MR2022.V24.N3-4.7