The lipid-protein film covering the interface of the lung alveolar in mammals is vital for proper lung function and its deficiency is related to a range of diseases. Here we present a molecular-level characterization of a clinical-grade porcine lung surfactant extract using a multitechnique approach consisting of [Formula: see text]-[Formula: see text] solid-state nuclear magnetic spectroscopy, small- and wide-angle X-ray scattering, and mass spectrometry. The detailed characterization presented for reconstituted membranes of a lung extract demonstrates that the molecular structure of lung surfactant strongly depends on the concentration of cholesterol. If cholesterol makes up about 11% of the total dry weight of lung surfactant, the surfactant extract adopts a single liquid-ordered lamellar phase, [Formula: see text], at physiological temperatures. This [Formula: see text] phase gradually changes into a liquid-disordered lamellar phase, [Formula: see text], when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar gel phase and one [Formula: see text] phase. Remarkably, it was possible to measure a large set of order parameter magnitudes [Formula: see text] from the liquid-disordered and -ordered lamellar phases and assign them to specific C-H bonds of the phospholipids in the biological extract with no use of isotopic labeling. These findings with molecular details on lung surfactant mixtures together with the presented NMR methodology may guide further development of pulmonary surfactant pharmaceuticals that better mimic the physiological self-assembly compositions for treatment of pathological states such as respiratory distress syndrome.
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http://dx.doi.org/10.1073/pnas.1701239114 | DOI Listing |
J Aerosol Med Pulm Drug Deliv
January 2025
Department of Mechanical Engineering, University of Alberta, Edmonton, Canada.
Dry powders offer the potential to increase stability and reduce cold-chain requirements associated with the distribution of vaccines and other thermally sensitive products. The Alberta Idealized Nasal Inlet (AINI) is a representative geometry for characterization of nasal products that may prove useful in examining intranasal delivery of powders. Spray-dried trehalose powders were loaded at 10, 20, and 40 mg doses into active single-dose devices.
View Article and Find Full Text PDFToxicol Sci
January 2025
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, 08854.
Ozone is an urban air pollutant, known to cause lung injury and altered function. Using established models of acute (0.8 ppm, 3 h) and episodic (1.
View Article and Find Full Text PDFBMC Pediatr
January 2025
Department of Pediatrics II (Neonatology), Medical University of Innsbruck, Innsbruck, Austria.
Preterm infants are at high risk of developing respiratory distress syndrome (RDS). Mutations in the genes encoding for surfactant proteins B and C or the ATP-binding cassette transporter A3 (ABCA3) are rare but known to be associated with severe RDS and interstitial lung diseases. The exact prevalence of these mutations in the general population is difficult to determine, as they are usually studied in connection with clinical symptoms.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Pulmonary surfactant (PS) is one of the main treatment for neonates with respiratory distress syndrome (RDS). Budesonide has recently been studied as an additional treatment in such cases, but there is limited evidence supporting this. This study was implemented to determine the efficacy of PS combined with budesonide in premature infants.
View Article and Find Full Text PDFRespir Res
January 2025
Department of Obstetrics and Gynecology, C.S. Mott Center for Human Growth and Development, School of Medicine, Wayne State University, 275 E Hancock St, Rm 195, Detroit, MI, 48201, USA.
Current fetal alcohol spectrum disorders (FASD) studies primarily focus on alcohol's actions on the fetal brain although respiratory infections are a leading cause of morbidity/mortality in newborns. The limited studies examining the pulmonary adaptations in FASD demonstrate decreased surfactant protein A and alveolar macrophage phagocytosis, impaired differentiation, and increased risk of Group B streptococcal pneumonia with no study examining sexual dimorphism in adaptations. We hypothesized that developmental alcohol exposure in pregnancy will lead to sexually dimorphic fetal lung morphological and immune adaptations.
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