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

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.

The Effect of Modified Porcine Surfactant Alone or in Combination with Polymyxin B on Lung Homeostasis in LPS-Challenged and Mechanically Ventilated Adult Rats

“…It was stated that the complexing of endotoxin with a pulmonary surfactant may contribute to pathological changes observed in pneumonia and these changes have been attributed to surfactant alterations [ 20 ]. LPS interacts with all SPs [ 21 , 22 , 23 ] and phospholipids which promote destabilization of surfactant film [ 10 ]. LPS-induced lung injury is a widely used animal model to test treatment possibilities, however, literary data on the appropriate dose of LPS vary.…”

“…The in vitro studies clearly show that LPS binds to the pulmonary surfactant and prevents it from reaching low surface tension even at an LPS concentration of 1% [ 10 ]. In vivo, endotoxin-induced lung damage can be favorably affected by i.t.…”

“…Moreover, it is able to mimic the properties of SP-B [ 8 ] and increase the resistance of surfactant preparations. Its beneficial effect was observed in vitro [ 10 ] but also in vivo when the surfactant/PxB mixture has been effective in animals with ARDS due to serum albumin leakage into the alveolar space [ 9 ] or in newborn rabbits with LPS-induced lung injury [ 46 ]. Therefore, the surfactant/PxB mixture appears to be a suitable treatment for Gram-negative lung infections.…”

“…In addition to its antibiotic effect, due to its property to bridge and stabilize phospholipid membranes, it is able to mimic the functions of the surfactant protein B [ 8 ]. PxB has no adverse effect on the biophysical activity of the surfactant and moreover, improves the resistance of surfactant to albumin [ 9 ], meconium, and lipopolysaccharide [ 10 ] in vitro.…”

The Effect of Pulmonary Surfactant on the Airway Smooth Muscle After Lipopolysaccharide Exposure and its Mechanisms

“…It induces both pro-inflammatory and pro-oxidative pathways which are widely interrelated (Salvesen et al 2010). In addition to the effect induced by binding to TLR4, LPS interferes directly with the surfactant film, fluidizes it and leads to its damage (Kolomaznik et al 2018). The result is the damage of pulmonary tissue and alveolar-capillary membrane, influx and activation of neutrophils, protein leakage followed by respiratory failure as a part of acute respiratory distress syndrome (ARDS) (Nova et al 2019).…”