The anti‐inflammatory and antiviral properties of anionic pulmonary surfactant phospholipids

• Published in: Immunological reviews 2023-08, Vol.317 (1), p.166-186
• Main Authors: Numata, Mari, Kandasamy, Pitchaimani, Voelker, Dennis R.
• Format: Article
• Language: English
• Subjects: Alveoli; Animal models; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antiviral activity; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; antivirals; anti‐inflammatory treatment; COVID-19; Humans; Immune response; Immune system; Inflammation; Influenza A; Innate immunity; Lipids; Lung - metabolism; Lungs; Phosphatidylglycerol; Phosphatidylglycerols - pharmacology; Phosphatidylglycerols - therapeutic use; Phosphatidylinositol; Phospholipids; Phospholipids - metabolism; Proteins; pulmonary surfactant phospholipids; Pulmonary Surfactants - chemistry; Pulmonary Surfactants - metabolism; Pulmonary Surfactants - therapeutic use; Receptors; respiratory RNA viruses; RNA viruses; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Surfactants; TLR2 protein; TLR3 protein; TLR4 protein; Toll-Like Receptor 2; Toll-like receptors; Viral diseases; Viruses
• ISSN: 0105-2896; 1600-065X; 1600-065X
• DOI: 10.1111/imr.13207

Summary 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 the 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 antiviral 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.