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Int. J. Mol. Sci. 2018, 19(7), 1964; https://doi.org/10.3390/ijms19071964

The Perturbation of Pulmonary Surfactant by Bacterial Lipopolysaccharide and Its Reversal by Polymyxin B: Function and Structure

1
Martin Biomedical Center and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 01 Martin, Slovakia
2
Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, 832 32 Bratislava, Slovakia
*
Author to whom correspondence should be addressed.
Received: 1 June 2018 / Revised: 30 June 2018 / Accepted: 4 July 2018 / Published: 5 July 2018
(This article belongs to the Section Molecular Biophysics)
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Abstract

After inhalation, lipopolysaccharide (LPS) molecules interfere with a pulmonary surfactant, a unique mixture of phospholipids (PLs) and specific proteins that decreases surface tension at the air–liquid interphase. We evaluated the behaviour of a clinically used modified porcine pulmonary surfactant (PSUR) in the presence of LPS in a dynamic system mimicking the respiratory cycle. Polymyxin B (PxB), a cyclic amphipathic antibiotic, is able to bind to LPS and to PSUR membranes. We investigated the effect of PxB on the surface properties of the PSUR/LPS system. Particular attention was paid to mechanisms underlying the structural changes in surface-reducing features. The function and structure of the porcine surfactant mixed with LPS and PxB were tested with a pulsating bubble surfactometer, optical microscopy, and small- and wide-angle X-ray scattering (SAXS/WAXS). Only 1% LPS (w/w to surfactant PLs) prevented the PSUR from reaching the necessary low surface tension during area compression. LPS bound to the lipid bilayer of PSUR and disturbed its lamellar structure by swelling. The structural changes were attributed to the surface charge unbalance of the lipid bilayers due to LPS insertion. PxB acts as an inhibitor of structural disarrangement induced by LPS and restores original lamellar packing, as detected by polarised light microscopy and SAXS. View Full-Text
Keywords: pulmonary surfactant; surface activity; inhibition; lipopolysaccharide; polymyxin B; SAXS pulmonary surfactant; surface activity; inhibition; lipopolysaccharide; polymyxin B; SAXS
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Kolomaznik, M.; Liskayova, G.; Kanjakova, N.; Hubcik, L.; Uhrikova, D.; Calkovska, A. The Perturbation of Pulmonary Surfactant by Bacterial Lipopolysaccharide and Its Reversal by Polymyxin B: Function and Structure. Int. J. Mol. Sci. 2018, 19, 1964.

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