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Pulmonary surfactant kinetic

Anthony Sallese, Takuji Suzuki, Cormac McCarthy, James Bridges, Alyssa Filuta, Paritha Arumugam, Kenjiro Shima, Yan Ma, Matthew Wessendarp, Diane Black, Claudia Chalk, Brenna Carey, Bruce C Trapnell
Macrophages are critical to organ structure and function in health and disease. To determine mechanisms by which granulocyte/macrophage-colony stimulating factor (GM-CSF) signaling normally maintains surfactant homeostasis and how its disruption causes pulmonary alveolar proteinosis (PAP), we evaluated lipid composition in alveolar macrophages and lung surfactant, macrophage-mediated surfactant clearance kinetics/dynamics, and cholesterol-targeted pharmacotherapy of PAP in vitro and in vivo. Without GM-CSF signaling, surfactant-exposed macrophages massively accumulated cholesterol ester-rich lipid-droplets and surfactant had an increased proportion of cholesterol...
August 31, 2017: Scientific Reports
Ary Serpa Neto, Pedro P Z A Campos, Sabrine N T Hemmes, Lieuwe D Bos, Thomas Bluth, Marion Ferner, Andreas Güldner, Markus W Hollmann, Inmaculada India, Thomas Kiss, Rita Laufenberg-Feldmann, Juraj Sprung, Demet Sulemanji, Carmen Unzueta, Marcos F Vidal Melo, Toby N Weingarten, Anita M Tuip-de Boer, Paolo Pelosi, Marcelo Gama de Abreu, Marcus J Schultz
BACKGROUND: Postoperative pulmonary complications (PPCs) are common after major abdominal surgery. The kinetics of plasma biomarkers could improve identification of patients developing PPCs, but the kinetics may depend on intraoperative ventilator settings. OBJECTIVE: To test whether the kinetics of plasma biomarkers are capable of identifying patients who will develop PPCs, and whether the kinetics depend on the intraoperative level of positive end-expiratory pressure (PEEP)...
April 2017: European Journal of Anaesthesiology
Ioannis G Theodorou, Pakatip Ruenraroengsak, Andrew Gow, Stephan Schwander, Junfeng Jim Zhang, Kian Fan Chung, Teresa D Tetley, Mary P Ryan, Alexandra E Porter
Inhaled nanoparticles (NPs) have high-deposition rates in the alveolar region of the lung but the effects of pulmonary surfactant (PS) on nanoparticle bioreactivity are unclear. Here, the impact of PS on the stability and dissolution of ZnO nanowires (ZnONWs) was investigated, and linked with their bioreactivity in vitro with human alveolar epithelial type 1-like cells (TT1). Pre-incubation of ZnONWs with Curosurf® (a natural porcine PS) decreased their dissolution at acidic pH, through the formation of a phospholipid corona...
November 2016: Nanotoxicology
Matteo Nespeca, Chiara Giorgetti, Stefano Nobile, Ilaria Ferrini, Manuela Simonato, Giovanna Verlato, Paola Cogo, Virgilio Paolo Carnielli
BACKGROUND: It is unknown whether Whole-Body Hypothermia (WBH) affects pulmonary function. In vitro studies, at relatively low temperatures, suggest that hypothermia may induce significant changes to the surfactant composition. The effect of WBH on surfactant kinetics in newborn infants is unknown. We studied in vivo kinetics of disaturated-phosphatidylcholine (DSPC) in asphyxiated newborns during WBH and in normothermic controls (NTC) with no or mild asphyxia. Both groups presented no clinically apparent lung disease...
2016: PloS One
Aron B Fisher, Chandra Dodia, Elena M Sorokina, Haitao Li, Suiping Zhou, Tobias Raabe, Sheldon I Feinstein
The phospholipase A2(PLA2) activity of peroxiredoxin (Prdx)6 has important physiological roles in the synthesis of lung surfactant and in the repair of peroxidized cell membranes. These functions require the activity of a lysophospholipid acyl transferase as a critical component of the phospholipid remodeling pathway. We now describe a lysophosphatidylcholine acyl transferase (LPCAT) activity for Prdx6 that showed a strong preference for lysophosphatidylcholine (LPC) as the head group and for palmitoyl CoA in the acylation reaction...
April 2016: Journal of Lipid Research
Christina Moulakakis, Christine Steinhäuser, Dominika Biedziak, Katja Freundt, Norbert Reiling, Cordula Stamme
NF-κB transcription factors are key regulators of pulmonary inflammatory disorders and repair. Constitutive lung cell type- and microenvironment-specific NF-κB/inhibitor κBα (IκB-α) regulation, however, is poorly understood. Surfactant protein (SP)-A provides both a critical homeostatic and lung defense control, in part by immune instruction of alveolar macrophages (AMs) via clathrin-mediated endocytosis. The central endocytic proteins, clathrin heavy chain (CHC) and the clathrin adaptor protein (AP) complex AP2, have pivotal alternative roles in cellular homeostasis that are endocytosis independent...
July 2016: American Journal of Respiratory Cell and Molecular Biology
Dwaipayan Mukherjee, Alexandra Porter, Mary Ryan, Stephan Schwander, Kian Fan Chung, Teresa Tetley, Junfeng Zhang, Panos Georgopoulos
Increasing use of engineered nanomaterials (ENMs) in consumer products may result in widespread human inhalation exposures. Due to their high surface area per unit mass, inhaled ENMs interact with multiple components of the pulmonary system, and these interactions affect their ultimate fate in the body. Modeling of ENM transport and clearance in vivo has traditionally treated tissues as well-mixed compartments, without consideration of nanoscale interaction and transformation mechanisms. ENM agglomeration, dissolution and transport, along with adsorption of biomolecules, such as surfactant lipids and proteins, cause irreversible changes to ENM morphology and surface properties...
September 2015: Nanomaterials
Sara D'Aronco, Manuela Simonato, Luca Vedovelli, Aldo Baritussio, Giovanna Verlato, Stefano Nobile, Chiara Giorgetti, Matteo Nespeca, Virgilio P Carnielli, Paola E Cogo
BACKGROUND: Term newborns with pneumonia show a reduced pulmonary compliance due to multiple and ill-defined factors. Surfactant proteins' (SPs) changes could have a role in the reduced compliance but the matter is still unsettled. The aim of this study was to clarify the meaning of SPs changes during pneumonia in term newborns. METHODS: In 28 term ventilated newborns, 13 with pneumonia and 15 with no lung disease, we measured SP-B, SP-A, disaturated-phosphatidylcholine (DSPC), and total phospholipids (PL) concentrations in tracheal aspirates at intubation and close to extubation...
October 2015: Pediatric Research
Ioannis G Theodorou, Danielle Botelho, Stephan Schwander, Junfeng Zhang, Kian Fan Chung, Teresa D Tetley, Milo S P Shaffer, Andrew Gow, Mary P Ryan, Alexandra E Porter
The increase of production volumes of silver nanowires (AgNWs) and of consumer products incorporating them may lead to increased health risks from occupational and public exposures. There is currently limited information about the putative toxicity of AgNWs upon inhalation and incomplete understanding of the properties that control their bioreactivity. The lung lining fluid (LLF), which contains phospholipids and surfactant proteins, represents a first contact site with the respiratory system. In this work, the impact of dipalmitoylphosphatidylcholine (DPPC), Curosurf, and murine LLF on the stability of AgNWs was examined...
July 7, 2015: Environmental Science & Technology
Ornpreya Suptawiwat, Chompunuch Boonarkart, Warunya Chakritbudsabong, Mongkol Uiprasertkul, Pilaipan Puthavathana, Witthawat Wiriyarat, Prasert Auewarakul
N-linked glycosylation of the influenza virus hemagglutinin (HA) protein plays crucial roles in HA structure and function, evasion of neutralizing antibodies, and susceptibility to innate soluble antiviral factors. The N-linked glycosylation site at position 158 of highly pathogenic H5N1 virus was previously shown to affect viral receptor-binding preference. H5N1 viruses show heterogeneity with respect to the presence of this glycosylation site. Clade 1 viruses that caused outbreaks in Southeast Asia in 2004 contained this glycosylation site, while the site is absent in the more recent clade 2 viruses...
February 2015: Archives of Virology
Keiichi Akasaka, Takahiro Tanaka, Takashi Maruyama, Nobutaka Kitamura, Atsushi Hashimoto, Yuko Ito, Hiroyoshi Watanabe, Tomoshige Wakayama, Takero Arai, Masachika Hayashi, Hiroshi Moriyama, Kanji Uchida, Shinya Ohkouchi, Ryushi Tazawa, Toshinori Takada, Etsuro Yamaguchi, Toshio Ichiwata, Masaki Hirose, Toru Arai, Yoshikazu Inoue, Hirosuke Kobayashi, Koh Nakata
Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar proteinosis (PAP), a process in which accumulated surfactants are washed out of the lung with 0.5-2.0 l of saline aliquots for 10-30 wash cycles. The method has been established empirically. In contrast, the kinetics of protein transfer into the lavage fluid has not been fully evaluated either theoretically or practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We made accurate timetables for each stage of WLL, namely, instilling, retaining, draining, and preparing...
January 15, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Alejandro Cerrada, Paz de la Torre, Jesús Grande, Thomas Haller, Ana I Flores, Jesús Pérez-Gil
Lung alveolar type II (ATII) cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs) have been differentiated into Alveolar Type II- Like Cells (ATII-LCs), which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark...
2014: PloS One
Nicolas de Prost, Yan Feng, Tyler Wellman, Mauro R Tucci, Eduardo L Costa, Guido Musch, Tilo Winkler, R Scott Harris, Jose G Venegas, Wei Chao, Marcos F Vidal Melo
UNLABELLED: PET with (18)F-FDG allows for noninvasive assessment of regional lung metabolism reflective of neutrophilic inflammation. This study aimed at determining during early acute lung injury whether local (18)F-FDG phosphorylation rate and volume of distribution were sensitive to the initial regional inflammatory response and whether they depended on the mechanism of injury: endotoxemia and surfactant depletion. METHODS: Twelve sheep underwent homogeneous unilateral surfactant depletion (alveolar lavage) and were mechanically ventilated for 4 h (positive end-expiratory pressure, 10 cm H2O; plateau pressure, 30 cm H2O) while receiving intravenous endotoxin (lipopolysaccharide-positive [LPS+] group; n = 6) or not (lipopolysaccharide-negative group; n = 6)...
November 2014: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Manuela Simonato, Aldo Baritussio, Barbara Pioselli, Carlo Ori, Silvia Catinella, Virgilio P Carnielli, Paola E Cogo
Surfactant protein C (SP-C) is deemed as the surfactant protein most specifically expressed in type II alveolar epithelial cells and plays an important role in surfactant function. SP-C turnover in humans and its meaning in the clinical context have never been approached. In this study, we used mass spectrometry to investigate SP-C turnover in humans. We studied four infants and eight adults requiring mechanical ventilation. All patients had no lung disease. Patients received a 24-h continuous infusion of (13)C-leucine as precursor of SP-C, and serial tracheal aspirates and plasma samples were obtained every 6 h till 48 h...
October 2014: Analytical and Bioanalytical Chemistry
Phuc Nghia Nguyen, Mariam Veschgini, Motomu Tanaka, Gilles Waton, Thierry Vandamme, Marie Pierre Krafft
Perfluorohexane gas lowers the kinetic barrier that opposes the displacement of albumin by dipalmitoylphosphatidylcholine at the air/water interface submitted to sinusoidal oscillations at frequencies in the range of those encountered in respiration.
October 9, 2014: Chemical Communications: Chem Comm
Catarina A Carvalheda, Sara R R Campos, Miguel Machuqueiro, António M Baptista
The pulmonary surfactant protein C (SP-C) is a small highly hydrophobic protein that adopts a mainly helical structure while associated with the membrane but misfolds into a β-rich metastable structure upon deacylation, membrane dissociation, and exposure to the neutral pH of the aqueous alveolar subphase, eventually leading to the formation of amyloid aggregates associated with pulmonary alveolar proteinosis. The present constant-pH MD study of the acylated and deacylated isoforms of SP-C in a chloroform/methanol/water mixture, often used to mimic the membrane environment, shows that the loss of the acyl groups has a structural destabilizing effect and that the increase of pH promotes intraprotein contacts which contribute to the loss of helical structure in solution...
November 25, 2013: Journal of Chemical Information and Modeling
Saija Taponen, Johanna M Huusko, Ulla E Petäjä-Repo, Reija Paananen, Susan H Guttentag, Mikko Hallman, Ritva Haataja
BACKGROUND: Surfactant protein B (SP-B) is essential for normal lung function, and decreased concentrations of SP-B have a deleterious effect on pulmonary outcome. SP-B levels may correlate with variations in the encoding gene (SFTPB). SFTPB single-nucleotide polymorphism Ile131Thr affects proSP-B N-glycosylation in humans and the glycosylated Thr variant associates with pulmonary diseases. METHODS: We analyzed SP-B levels in amniotic fluid samples for associations with SFTPB polymorphisms and generated cell lines expressing either proSP-B/131Ile or proSP-B/131Thr for examining the effect of glycosylation on proSP-B secretion kinetics...
December 2013: Pediatric Research
Bey Fen Leo, Shu Chen, Yoshihiko Kyo, Karla-Luise Herpoldt, Nicholas J Terrill, Iain E Dunlop, David S McPhail, Milo S Shaffer, Stephan Schwander, Andrew Gow, Junfeng Zhang, Kian Fan Chung, Teresa D Tetley, Alexandra E Porter, Mary P Ryan
The growing use of silver nanoparticles (AgNPs) in consumer products has raised concerns about their potential impact on the environment and human health. Whether AgNPs dissolve and release Ag(+) ions, or coarsen to form large aggregates, is critical in determining their potential toxicity. In this work, the stability of AgNPs in dipalmitoylphosphatidylcholine (DPPC), the major component of pulmonary surfactant, was investigated as a function of pH. Spherical, citrate-capped AgNPs with average diameters of 14 ± 1...
October 1, 2013: Environmental Science & Technology
Ala'a F Eftaiha, Sophie M K Brunet, Matthew F Paige
Monolayer surfactant films composed of a mixture of phospholipids and perfluorinated (or partially fluorinated) surfactants are of potential utility for applications in pulmonary lung surfactant-based therapies. As a simple, minimal model of such a lung surfactant system, binary mixed monolayer films composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and perfluorooctadecanoic acid (C18F) prepared on a simplified lung fluid mimic subphase (pH 7.4, 150 mM NaCl) have been characterized in terms of mixing thermodynamics and compressibility (measured through π–A compression isotherms), film morphology (via atomic force, fluorescence, and Brewster angle microscopy), as well as spreading rate and hysteresis response to repeated expansion–contraction cycles for a variety of compositions of mixed films...
October 30, 2012: Langmuir: the ACS Journal of Surfaces and Colloids
Mohammad Ariful Islam, Muhammad Jasim Uddin, Ernst Tholen, Dawit Tesfaye, Christian Looft, Karl Schellander, Mehmet Ulas Cinar
The aim of the present study was to determine the age-related changes of phagocytic capacity and the kinetic production of cytokines in lipopolysaccharide-stimulated porcine alveolar macrophages. For this purpose, AMs were isolated from 5 (newborn), 40 (post-weaned) and 120 (young) day old pigs. Results of phagocytosis assay showed that AMs from newborn piglets had less phagocytic capacity than those of young pigs (P<0.05). For the kinetics study, cells and supernatant were collected at 1, 6, 12, 24, 36 and 48 h after LPS stimulation for quantification of cytokine mRNA and protein by quantitative real-time PCR and ELISA, respectively...
December 2012: Cytokine
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