The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections

Abstract

Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension-lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications.

Keywords: immune responses; infection; pulmonary host defense; surfactant.

Figure 1.

The composition and function of surfactant. Surfactant is composed of 90% lipid and 10% protein. The lipid content contains primarily phospholipid, specifically dipalmitoylphosphatidylcholine, which is responsible for the biophysical function of surfactant. The large hydrophilic proteins, surfactant protein (SP)-A and SP-D, play an important role in host defense and immune modulation, whereas SP-B and SP-C primarily partake in modulating biophysical properties.

Figure 2.

Surfactant life cycle—synthesis, secretion, and recycling. Alveolar type II cells, which cover about 7% of alveolar epithelial surface, are mainly responsible for surfactant production using dietary substrates (1). Surfactant is synthesized in the endoplasmic reticulum (ER) (2) of alveolar type II cells, and transported to the Golgi (3) for further modification. Most of the surfactant components are stored in the lamellar bodies (4) until they are secreted into liquid hypophase on the alveoli by exocytosis (5). Surfactant forms a lattice-like structure, called tubular myelin (6), which is transported to the air–liquid interface to form a monolayer of surfactant film (7). The phospholipids are either internalized and degraded by macrophages (8) or recycled back to the type II cells for reuse (8′). Note that surfactant protein (SP)-A, SP-B, and SP-D are also synthesized in club cells in terminal bronchioles.