The Potential Role of Bioactive Plasmalogens in Lung Surfactant

Abstract

Neonatal respiratory distress syndrome (NRDS) is a type of newborn disorder caused by the deficiency or late appearance of lung surfactant, a mixture of lipids and proteins. Studies have shown that lung surfactant replacement therapy could effectively reduce the morbidity and mortality of NRDS, and the therapeutic effect of animal-derived surfactant preparation, although with its limitations, performs much better than that of protein-free synthetic ones. Plasmalogens are a type of ether phospholipids present in multiple human tissues, including lung and lung surfactant. Plasmalogens are known to promote and stabilize non-lamellar hexagonal phase structure in addition to their significant antioxidant property. Nevertheless, they are nearly ignored and underappreciated in the lung surfactant-related research. This report will focus on plasmalogens, a minor yet potentially vital component of lung surfactant, and also discuss their biophysical properties and functions as anti-oxidation, structural modification, and surface tension reduction at the alveolar surface. At the end, we boldly propose a novel synthetic protein-free lung surfactant preparation with plasmalogen modification as an alternative strategy for surfactant replacement therapy.

Coronavirus-Induced Host Cubic Membranes and Lipid-Related Antiviral Therapies: A Focus on Bioactive Plasmalogens

“…Interestingly, the alveolar macrophages do not kill in vitro the pathogens unless the latter have been incubated with alveolar lining material (i.e., lung surfactant) before their phagocytosis. Although plasmalogens in lung surfactant are not the major components of the phospholipid mixture, they have been reported to significantly reduce surface viscosity and surface tension (Rüdiger et al, 1998(Rüdiger et al, , 2005Zhuo et al, 2021). The role of plasmalogens in facilitating membrane fusion has been well recognized (Marrink and Mark, 2004).…”

“…This ether phospholipid, together with cholesterol and surfactant-associated proteins, regulate the surfactant monolayer stability and viscosity. Another key feature is that plasmalogens act as antioxidants and protect alveolar cells from oxidative stress that often encountered at alveolar surface (Zhuo et al, 2021). Plasmalogens may contribute to substantial lowering the surface tension (Rüdiger et al, 1998) and viscosity (Rüdiger et al, 2005) of the lipid mixture.…”

Plasmalogenic Lipid Analogs as Platelet-Activating Factor Antagonists: A Potential Novel Class of Anti-inflammatory Compounds

“…Figure 1 summarizes a variety of proposed biological functions for plasmalogens as antioxidants in addition to their modulatory role in membrane structure and dynamics ( Bozelli et al, 2021 ). The high susceptibility of the vinyl-ether bond at sn-1 position to radicals including reactive oxygen species (ROS) and reactive nitrogen species (RNS) as well as to the traces of acids supports their important role as a first-line defense system in biology against oxidative damages ( Zhuo et al, 2021 ; Bozelli et al, 2021 ). Previously, Deng and colleagues have proposed that plasmalogens carrying PUFA chains may promote intracellular cubic membranes (CM) formation ( Deng et al, 2009 ) with the implication in virus-induced host CM formation ( Deng et al, 2010 ; Deng and Angelova, 2021 ).…”

“…It has been reported that plasmalogens are highly concentrated in lipid bilayer microdomains in cellular and subcellular organelle membranes ( Messias et al, 2018 ). They naturally participate in multiple cellular processes including membrane fusion ( Zhuo et al, 2021 ), cholesterol homeostasis ( Honsho et al, 2015 ), ion transport ( Messias et al, 2018 ) and immunomodulation ( Deng and Angelova, 2021 ). In lipid biosynthesis, plasmalogens can be the source of supply for the precursor of PAF ( Dorninger et al, 2020 ) ( Figure 1 ).…”

“…The interest in new classes of lipid-based anti-inflammatory drugs constantly increases in view of their critical role in the strategies to inhibit the inflammatory component of the coronavirus SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) infection ( Casari et al, 2021 ; Deng and Angelova, 2021 ; Schwarz et al, 2021 ), modulation of respiratory distress diseases ( Mirastschijski et al, 2020 ; Zhuo et al, 2021 ) as well as in cancer and diabetes ( Paul et al, 2019 ), and neuro-inflammation ( Ifuku et al, 2012 ). Plasmalogens exert anti-inflammatory effects and have been first described by Feulgen and Voit in 1924 in relation to their characteristic production of aldehydes in acidic environment ( Rapport, 1984 ).…”