Potential Therapeutic Applications of Pulmonary Surfactant Lipids in the Host Defence Against Respiratory Viral Infections

Abstract

Pulmonary surfactant is a complex and highly surface-active material. It covers the alveolar epithelium and consists of 90% lipids and 10% proteins. Pulmonary surfactant lipids together with pulmonary surfactant proteins facilitate breathing by reducing surface tension of the air-water interface within the lungs, thereby preventing alveolar collapse and the mechanical work required to breathe. Moreover, pulmonary surfactant lipids, such as phosphatidylglycerol and phosphatidylinositol, and pulmonary surfactant proteins, such as surfactant protein A and D, participate in the pulmonary host defense and modify immune responses. Emerging data have shown that pulmonary surfactant lipids modulate the inflammatory response and antiviral effects in some respiratory viral infections, and pulmonary surfactant lipids have shown promise for therapeutic applications in some respiratory viral infections. Here, we briefly review the composition, antiviral properties, and potential therapeutic applications of pulmonary surfactant lipids in respiratory viral infections.

Keywords: ARDS; COVID-19; pulmonary surfactant lipids; respiratory viral infections; therapeutic applications.

Figure 1

Pulmonary surfactant lipid constituents. Pulmonary surfactant components are important lipoprotein complexes of the lung lining, consisting of 90% lipids and 10% proteins by weight. Pulmonary surfactant proteins contain four proteins, including surfactant protein (SP)-A, SP-B, SP-C, and SP-D. In pulmonary surfactant lipids, the most abundant constituents are glycerophospholipids. Surfactant phospholipids (PLs) account for 80–85% of pulmonary surfactant lipids; surfactant PLs are a mixture of lipids, which include phosphatidylcholine (PC, accounting for about 80%), phosphatidylglycerol (PG, accounting for about 7–15%), and small quantities (accounting for approximately 5% each) of phosphatidylinositol (PI), phosphatidylethanolamine (PE), and phosphatidylserine (PS). The most prevalent PL in pulmonary surfactant is PC, and approximately 40% of surfactant PC is saturated dipalmitoyl-PC (DPPC).

Figure 2

Potential mechanism of PLs in therapeutic applications in respiratory viral infections. Respiratory viral infections can induce the dysfunction of pulmonary surfactant lipids. Supplement the pulmonary surfactant lipids may have therapeutic effects as follows: it may (1) supplement the decreased pulmonary surfactant lipids; (2) reduce surface tension and prevent alveolar collapse during respiratory activity; (3) inhibit the proinflammatory response and alleviate tissue damage in lungs; and (4) inhibit virus replications and limit virus infection.