The anti-inflammatory and anti-viral properties of anionic pulmonary surfactant phospholipids

• Published in: Immunological reviews 2023-05, Vol.317 (1), p.166-186
• Main Authors: Numata, Mari, Kandasamy, Pitchaimani, Voelker, Dennis R.
• Format: Article
• Language: English
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.13207

The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse, and the innate immune system in the lung. Pulmonary surfactant is a lipoprotein complex consisting of 90% phospholipids and 10% protein, by weight. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), exist at very high concentrations in the extracellular alveolar compartments. We have reported that one of most dominant molecular species of PG, palmitoyl-oleoyl phosphatidylglycerol (POPG) and PI inhibit inflammatory responses induced by multiple Toll-like receptors (TLR2/1, TLR3, TLR4, and TLR2/6) by interacting with subsets of multiprotein receptor components. These lipids also exert potent anti-viral effects against RSV and influenza A, in vitro, by inhibiting virus binding to host cells. POPG and PI inhibit these viral infections in vivo, in multiple animal models. Especially noteworthy, these lipids markedly attenuate SARS-CoV-2 infection including its variants. These lipids are natural compounds that already exist in the lung, and thus are less likely to cause adverse immune responses by hosts. Collectively, these data demonstrate that POPG and PI have strong potential as novel therapeutics for applications as anti-inflammatory compounds and preventatives, as treatments for broad ranges of RNA respiratory viruses.