Commercial versus Native Surfactants

Bernhard, Wolfgang; Mottaghian, J.; Gebert, Andreas; Rau, Gunnar A.; Hardt, H. von der; Poets, Christian F.

doi:10.1164/ajrccm.162.4.9908104

Cited by 188 publications

(135 citation statements)

References 44 publications

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“…The overall compositions of the lipid extracts of BAL and extracts from minced lungs extracts are similar with only small differences in phospholipid composition (56). The hydrophilic proteins (SP-A and SP-D) are not present in any of the two extract types due to the low solubility in the organic solvents.…”

Section: Resultsmentioning

confidence: 86%

“…The surfactant is extracted from minced porcine lungs by the method of Bligh and Dyer (55). After extraction only the hydrophobic surfactant proteins (SP-B and SP-C) are present in the LSE, at a concentration of 1 to 2% each, with complete removal of the hydrophilic surfactant proteins (56,61). The 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), POPC, 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG), and cholesterol were purchased from Avanti Polar Lipids.…”

Section: Methodsmentioning

confidence: 99%

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Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Andersson

Grey

Larsson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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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 1 H-13 C 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, L α(o) , at physiological temperatures. This L α(o) phase gradually changes into a liquid-disordered lamellar phase, L α(d) , when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar gel phase and one L α(d) phase. Remarkably, it was possible to measure a large set of order parameter magnitudes |S CH | from the liquiddisordered 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 selfassembly compositions for treatment of pathological states such as respiratory distress syndrome.T he air-alveoli interface of human lungs consists of ∼100 m 2 of surface area covered by a 1-to 2-µm-thick film rich in lipids, generally referred to as lung surfactant (LS) (1, 2). The alveolar interfacial film has several important functions, including stabilizing the interface, allowing for area expansions and controlling diffusional transport (3-7). These functions strongly rely on the self-assembly structure, as well as on the mechanical, barrier, and surface properties of the dynamic LS interfacial layer, which in turn depend on its chemical composition and external conditions in terms of compression, hydration, and so on. The main components of LS are phospholipids, cholesterol, and the so-called surfactant proteins representing ∼80, 10, and 10 wt %, respectively (2).Deficiency of LS in the alveoli, or an imbalance of its chemical composition, induces a number of pathological conditions (8). For instance, neonatal respiratory distress syndrome affects prematurely born infants when LS is not yet matured or is completely lacking; this deficiency may be lethal if left untreated. In these cases, the most common treatment is intratracheal administration of an exogenous LS into the lungs (9). In case of acute respiratory distress syndrome the mortality is 35 to 45% (10) and an effective treatment is clearly lacking (8). An accurate characterization of the molecular structure and dynamics of endogenous an...

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Section: Resultsmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Andersson

Grey

Larsson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…It is found that all three proteins promote fusion of the unilamellar micelles into larger multilamellar micelles, in good agreement with experimental observations of the ultrastructure of protein-containing natural PS. 15,34 Specifically, it is found that the hydrophobic SP-B (in orange) and SP-C (in purple) mainly assume transmembrane positions, whereas the hydrophilic SP-A (in violet) locates primarily at the intermembrane space to bridge individual micelles. In general, results of our MD simulations are in good agreement with the current molecular understanding and predication of lipid− protein interactions in natural PS vesicles and films.…”

Section: Resultsmentioning

confidence: 99%

Unveiling the Molecular Structure of Pulmonary Surfactant Corona on Nanoparticles

et al. 2017

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The growing risk of human exposure to airborne nanoparticles (NPs) causes a general concern on the biosafety of nanotechnology. Inhaled NPs can deposit in the deep lung at which they interact with the pulmonary surfactant (PS). Despite the increasing study of nano-bio interactions, detailed molecular mechanisms by which inhaled NPs interact with the natural PS system remain unclear. Using coarse-grained molecular dynamics simulation, we studied the interaction between NPs and the PS system in the alveolar fluid. It was found that regardless of different physicochemical properties, upon contacting the PS, both silver and polystyrene NPs are immediately coated with a biomolecular corona that consists of both lipids and proteins. Structure and molecular conformation of the PS corona depend on the hydrophobicity of the pristine NPs. Quantitative analysis revealed that lipid composition of the corona formed on different NPs is relatively conserved and is similar to that of the bulk phase PS. However, relative abundance of the surfactant-associated proteins, SP-A, SP-B, and SP-C, is notably affected by the hydrophobicity of the NP. The PS corona provides the NPs with a physicochemical barrier against the environment, equalizes the hydrophobicity of the pristine NPs, and may enhance biorecognition of the NPs. These modifications in physicochemical properties may play a crucial role in affecting the biological identity of the NPs and hence alter their subsequent interactions with cells and other biological entities. Our results suggest that all studies of inhalation nanotoxicology or NP-based pulmonary drug delivery should consider the influence of the PS corona.

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“…Alveofact (Boehringer Ingelheim, Ingelheim am Rhein, Germany) is an organic solvent extract of a fraction isolated from cow lung lavage. It contains 88% phospholipids, 4% cholesterol, 8% other lipids and 1% hydrophobic proteins (SP-B, SP-C) [17]. In addition, a synthetic surfactant preparation (Venticute; Nycomed Deutschland GmbH, formerly Altana Pharma AG) was used which is well characterized and consists of 63.4% 2-dipalmitoyl-sn-glycero-3-phosphocholine, 27.8% 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, 4.5% palmitic acid, 2.5% calcium chloride and 1.8% recombinant SP-C (lusupultide) [18].…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Surfactants Modulate the Viability of Eosinophils and Induce Inflammatory Mediator Release

Erpenbeck

Fischer

Wiese

et al. 2009

Int Arch Allergy Immunol

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Background: There is increasing interest in testing surfactant preparations for asthma therapy. Previously, Curosurf was demonstrated to increase inflammation in allergic asthmatics. So far, little is known about the immunomodulatory effects of therapeutic surfactants, in particular concerning the interaction of surfactant components with eosinophils as key effector cells of the allergic airway inflammation. The aim of the present study was to determine the effect of different therapeutic surfactants on cellular functions of eosinophils. Methods: Eosinophils were isolated from peripheral blood of atopic volunteers and incubated with the natural animal-derived surfactants Curosurf or Alveofact or the synthetic recombinant human surfactant Venticute at different concentrations for up to 42 h. Results: Curosurf and Venticute modulated the viability of eosinophils. While incubation with Curosurf increased the number of necrotic eosinophils after 1, 20 and 42 h, Venticute increased the number of apoptotic and necrotic cells after 1 h, but there were no differences compared with control cells at later time points. All surfactant preparations increased the levels of eosinophil cationic protein after 20 h and, in addition, Curosurf enhanced eosinophil cationic protein release after 42 h. The supernatant of eosinophils induced chemotaxis against autologous eosinophils, and the presence of Curosurf, but not Alveofact or Venticute, augmented the chemotactic effect. Chemotaxis was partly blocked by inhibition of eotaxin but not by inhibition of leukotrienes or platelet-activating factor. Conclusions: Therapeutic surfactants differ in their effects on eosinophil viability and the accompanying release of inflammatory mediators and chemotactic signals. Proinflammatory effects were most pronounced for the natural surfactant Curosurf.

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Commercial versus Native Surfactants

Cited by 188 publications

References 44 publications

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Unveiling the Molecular Structure of Pulmonary Surfactant Corona on Nanoparticles

Therapeutic Surfactants Modulate the Viability of Eosinophils and Induce Inflammatory Mediator Release

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