Current perspectives in pulmonary surfactant — Inhibition, enhancement and evaluation

Abstract

Pulmonary surfactant (PS) is a complicated mixture of approximately 90% lipids and 10% proteins. It plays an important role in maintaining normal respiratory mechanics by reducing alveolar surface tension to near-zero values. Supplementing exogenous surfactant to newborns suffering from respiratory distress syndrome (RDS), a leading cause of perinatal mortality, has completely altered neonatal care in industrialized countries. Surfactant therapy has also been applied to the acute respiratory distress syndrome (ARDS) but with only limited success. Biophysical studies suggest that surfactant inhibition is partially responsible for this unsatisfactory performance. This paper reviews the biophysical properties of functional and dysfunctional PS. The biophysical properties of PS are further limited to surface activity, i.e., properties related to highly dynamic and very low surface tensions. Three main perspectives are reviewed. (1) How does PS permit both rapid adsorption and the ability to reach very low surface tensions? (2) How is PS inactivated by different inhibitory substances and how can this inhibition be counteracted? A recent research focus of using water-soluble polymers as additives to enhance the surface activity of clinical PS and to overcome inhibition is extensively discussed. (3) Which in vivo, in situ, and in vitro methods are available for evaluating the surface activity of PS and what are their relative merits? A better understanding of the biophysical properties of functional and dysfunctional PS is important for the further development of surfactant therapy, especially for its potential application in ARDS.

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

“…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 and exogenous lung surfactant, together with relating such molecular properties with LS functions, should aid significantly in the development of more efficient treatments.…”

Unveiling the Molecular Structure of Pulmonary Surfactant Corona on Nanoparticles

“…18,33 Consequently, a physiological level of cholesterol helps solidify the PS membranes, but a supraphysiological level of cholesterol deteriorates the biophysical function of PS by fluidizing the surfactant vesicles and films. 18,33 Figure 1b shows the self-assembled PS ultrastructure with the addition of three membrane-binding surfactant proteins, such as SP-B, SP-C, and SP-A (the dynamic process of PS selfassembly can be found in Video S2 of the Supporting Information). 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.…”

“…15−17 The PS is composed of approximately 90% lipids, including various phospholipids and cholesterol, and 10% proteins (named SP-A, SP-B, SP-C, and SP-D) by weight. 18 Among these four surfactant-associated proteins, SP-B and SP-C are small hydrophobic membrane proteins that are essentially important for reducing alveolar surface tensions and thus indispensable for sustaining normal respiratory physiology. 19 SP-A and SP-D are large hydrophilic proteins and members of the collectin family, which play an important role in innate host defense by binding inhaled particles and pathogens.…”

The Influence of Natural Pulmonary Surfactant on The Efficacy of siRNA-Loaded Dextran Nanogels

“…Subsequently, equal volumes of DEX-NG dilutions and siRNA were mixed and incubated at 4°C for ≥ 15 min to allow complexation. protein compositions can be found in the literature [11,20,21].…”