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Frontiers in Immunology 2023Pulmonary surfactant (PS), a complex mixture of lipids and proteins, is essential for maintaining proper lung function. It reduces surface tension in the alveoli,... (Review)
Review
Pulmonary surfactant (PS), a complex mixture of lipids and proteins, is essential for maintaining proper lung function. It reduces surface tension in the alveoli, preventing collapse during expiration and facilitating re-expansion during inspiration. Additionally, PS has crucial roles in the respiratory system's innate defense and immune regulation. Dysfunction of PS contributes to various respiratory diseases, including neonatal respiratory distress syndrome (NRDS), adult respiratory distress syndrome (ARDS), COVID-19-associated ARDS, and ventilator-induced lung injury (VILI), among others. Furthermore, PS alterations play a significant role in chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). The intracellular stage involves storing and releasing a specialized subcellular organelle known as lamellar bodies (LB). The maturation of these organelles requires coordinated signaling to organize their intracellular organization in time and space. LB's intracellular maturation involves the lipid composition and critical processing of surfactant proteins to achieve proper functionality. Over a decade ago, the supramolecular organization of lamellar bodies was studied using electron microscopy. In recent years, novel bioimaging tools combining spectroscopy and microscopy have been utilized to investigate the intracellular organization of lamellar bodies temporally and spatially. This short review provides an up-to-date understanding of intracellular LBs. Hyperspectral imaging and phasor analysis have allowed identifying specific transitions in LB's hydration, providing insights into their membrane dynamics and structure. A discussion and overview of the latest approaches that have contributed to a new comprehension of the trafficking and structure of lamellar bodies is presented.
Topics: Adult; Infant, Newborn; Humans; Pulmonary Surfactants; COVID-19; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
PubMed: 37638003
DOI: 10.3389/fimmu.2023.1250350 -
Chest Apr 2023
Topics: Humans; Pulmonary Fibrosis; Surface-Active Agents; Pulmonary Surfactants; Mutation
PubMed: 37031979
DOI: 10.1016/j.chest.2022.12.020 -
Clinics in Perinatology Dec 2016Respiratory distress syndrome (RDS) caused by surfactant deficiency is major cause for neonatal mortality and short- and long-term morbidity of preterm infants.... (Review)
Review
Respiratory distress syndrome (RDS) caused by surfactant deficiency is major cause for neonatal mortality and short- and long-term morbidity of preterm infants. Continuous positive airway pressure and other modes of noninvasive respiratory support and intubation and positive pressure ventilation with surfactant therapy are efficient therapies for RDS. Because continuous positive airway pressure can fail in severe surfactant deficiency, and because traditional surfactant therapy requires intubation and positive pressure ventilation, this entails a risk of lung injury. Several strategies to combine noninvasive respiratory therapy with minimally invasive surfactant therapy have been described. Available data suggest that those strategies may improve outcome of premature infants with RDS.
Topics: Catheterization; Humans; Infant, Newborn; Infant, Premature; Laryngeal Masks; Nebulizers and Vaporizers; Noninvasive Ventilation; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 27837757
DOI: 10.1016/j.clp.2016.07.010 -
Environmental Science & Technology Dec 2023Microplastics (MPs) are ubiquitous environmental pollutants produced through the degradation of plastic products. Nanoplastics (NPs), commonly coexisting with MPs in the...
Microplastics (MPs) are ubiquitous environmental pollutants produced through the degradation of plastic products. Nanoplastics (NPs), commonly coexisting with MPs in the environment, are submicrometer debris incidentally produced from fragmentation of MPs. We studied the biophysical impacts of MPs/NPs derived from commonly used commercial plastic products on a natural pulmonary surfactant extracted from calf lung lavage. It was found that in comparison to MPs/NPs derived from lunch boxes made of polypropylene or from drinking water bottles made of poly(ethylene terephthalate), the MP/NP derived from foam packaging boxes made of polystyrene showed the highest adverse impact on the biophysical function of the pulmonary surfactant. Accordingly, intranasal exposure of MP/NP derived from the foam boxes also induced the most serious proinflammatory responses and lung injury in mice. Atomic force microscopy revealed that NP particles were adsorbed on the air-water surface and heteroaggregated with the pulmonary surfactant film. These results indicate that although the incidentally formed NPs only make up a small mass fraction, they likely play a predominant role in determining the nano-bio interactions and the lung toxicity of MPs/NPs by forming heteroaggregates at the alveolar-capillary interface. These findings may provide novel insights into understanding the health impact of MPs and NPs on the respiratory system.
Topics: Animals; Mice; Pulmonary Surfactants; Microplastics; Plastics; Environmental Pollutants; Polypropylenes; Water Pollutants, Chemical
PubMed: 38055865
DOI: 10.1021/acs.est.3c06668 -
Pediatric Pulmonology Oct 2021Various less invasive surfactant administration strategies like surfactant replacement therapy via thin catheters, laryngeal mask airway, pharyngeal instillation, and... (Review)
Review
Various less invasive surfactant administration strategies like surfactant replacement therapy via thin catheters, laryngeal mask airway, pharyngeal instillation, and nebulized surfactant are increasingly being practiced to avoid the harmful effects of endotracheal intubation and ventilation. Numerous studies have been done to study surfactant replacement via thin catheters whereas little data is available for other methods. However, there are variations in premedication policies, type of respiratory support used in these studies. Surfactant delivery using thin catheters has been reported to be associated with decrease in the need for mechanical ventilation (MV), duration of MV, bronchopulmonary dysplasia and neonatal mortality. With the current evidence, among all the available surfactant delivery methods, the one using thin catheters appears to be the most feasible and beneficial to improve clinical neonatal outcomes.
Topics: Bronchopulmonary Dysplasia; Catheters; Humans; Infant, Newborn; Infant, Premature; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 34379878
DOI: 10.1002/ppul.25599 -
Human Gene Therapy Oct 2022Genetic disorders of surfactant dysfunction result in significant morbidity and mortality, among infants, children, and adults. Available medical interventions are... (Review)
Review
Genetic disorders of surfactant dysfunction result in significant morbidity and mortality, among infants, children, and adults. Available medical interventions are limited, nonspecific, and generally ineffective. As such, the need for effective therapies remains. Pathogenic variants in the , and genes, each of which encode proteins essential for proper pulmonary surfactant production and function, result in interstitial lung disease in infants, children, and adults, and lead to morbidity and early mortality. Expression of these genes is predominantly limited to the alveolar type 2 (AT2) epithelial cells present in the distal airspaces of the lungs, thus providing an unequivocal cellular origin of disease pathogenesis. While several treatment strategies are under development, a gene-based therapeutic holds great promise as a definitive therapy. Importantly for clinical translation, the genes associated with surfactant dysfunction are both well characterized and amenable to a gene-therapeutic-based strategy. This review focuses on the pathophysiology associated with these genetic disorders of surfactant dysfunction, and also provides an overview of the current state of gene-based therapeutics designed to target and transduce the AT2 cells.
Topics: Infant; Child; Adult; Humans; Pulmonary Surfactants; Lung Diseases, Interstitial; Lung; Epithelial Cells; Mutation; Alveolar Epithelial Cells
PubMed: 36166236
DOI: 10.1089/hum.2022.130 -
Biomaterials Advances Jul 2023Lung cancer is often diagnosed at an advanced stage where tumors are usually inoperable and first-line therapies are inefficient and have off-targeted adverse effects,...
Lung cancer is often diagnosed at an advanced stage where tumors are usually inoperable and first-line therapies are inefficient and have off-targeted adverse effects, resulting in poor patient survival. Here, we report the development of an inhalable poly lactic-co-glycolic acid polymer-based nanoparticle (PLGA-NP) formulation with a biomimetic Infasurf® lung surfactant (LS) coating, for localized and sustained lung cancer drug delivery. The nanoparticles (188 ± 7 nm) were stable in phosphate buffered saline, serum and Gamble's solution (simulated lung fluid), and demonstrated cytocompatibility up to 1000 μg/mL concentration and dose-dependent uptake by lung cancer cells. The LS coating significantly decreased nanoparticle (NP) uptake by NR8383 alveolar macrophages in vitro compared to uncoated NPs. The coating, however, did not impair NP uptake by A549 lung adenocarcinoma cells. The anti-cancer drug gemcitabine hydrochloride encapsulated in the PLGA core was released in a sustained manner while the paclitaxel loaded in the LS shell demonstrated a rapid or burst release profile over 21 days. The drug-loaded NPs significantly decreased cancer cell survival and colony formation in vitro compared to free drugs and single drug-loaded NPs. In vivo studies confirmed greater retention of LS-coated NPs in the lungs of C57BL/6 WT mice compared to uncoated NPs, at 24 h and 72 h following intranasal administration. The overall results confirm that LS coating is a unique strategy for cloaking polymeric NPs to potentially prevent their rapid lung clearance and facilitate prolonged pulmonary drug delivery.
Topics: Mice; Animals; Polymers; Polylactic Acid-Polyglycolic Acid Copolymer; Mice, Inbred C57BL; Lung; Lung Neoplasms; Pulmonary Surfactants; Nanoparticles; Surface-Active Agents
PubMed: 37104963
DOI: 10.1016/j.bioadv.2023.213430 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Aug 2016Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant... (Review)
Review
Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases.
Topics: ATP-Binding Cassette Transporters; DNA-Binding Proteins; Homeostasis; Humans; Lung Diseases; Pulmonary Surfactant-Associated Protein C; Pulmonary Surfactants; Transcription Factors
PubMed: 27455022
DOI: 10.3760/cma.j.issn.1003-9406.2016.04.031 -
Bulletin of the World Health... May 2023Treatment with surfactant has been found to improve the survival rate of neonates with respiratory distress syndrome, particularly preterm infants. However, surfactant... (Review)
Review
Treatment with surfactant has been found to improve the survival rate of neonates with respiratory distress syndrome, particularly preterm infants. However, surfactant is usually administered by endotracheal intubation and generally only in level-3 neonatal intensive care units. Recent improvements in aerosolization technology have raised the possibility that aerosolized surfactant could now be given in wider range of settings, including resource-poor settings. Consequently, the World Health Organization has developed a target product profile for product developers that describes the optimal and minimal characteristics of an aerosolized surfactant for treating neonates with respiratory distress syndrome in low- and middle-income countries. Development of the target product profile involved a scoping review of systematic reviews and target product profiles of aerosolized surfactant, the constitution of an international expert advisory group, consultations with medical professionals from a wide range of countries and a public consultation. The resulting target product profile specifies that the surfactant and its associated aerosolization device should ideally, among other characteristics: (i) be at least as safe and effective as current intratracheal surfactant; (ii) produce a rapid clinical improvement; (iii) be easy to transport and use (e.g. by nurses in level-2 health-care facilities in low- and middle-income countries); (iv) be affordable for low- and middle-income countries; and (v) be stable when stored in hot and humid conditions. In addition, the aerosolization device should be capable of daily use for many years. The introduction of an effective aerosolized surfactant globally could substantially reduce neonatal mortality due to respiratory distress syndrome.
Topics: Infant; Infant, Newborn; Humans; Surface-Active Agents; Infant, Premature; Systematic Reviews as Topic; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 37131945
DOI: 10.2471/BLT.23.289727 -
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