Alveolar lipids in pulmonary disease. A review

Abstract

Lung lipid metabolism participates both in infant and adult pulmonary disease. The lung is composed by multiple cell types with specialized functions and coordinately acting to meet specific physiologic requirements. The alveoli are the niche of the most active lipid metabolic cell in the lung, the type 2 cell (T2C). T2C synthesize surfactant lipids that are an absolute requirement for respiration, including dipalmitoylphosphatidylcholine. After its synthesis and secretion into the alveoli, surfactant is recycled by the T2C or degraded by the alveolar macrophages (AM). Surfactant biosynthesis and recycling is tightly regulated, and dysregulation of this pathway occurs in many pulmonary disease processes. Alveolar lipids can participate in the development of pulmonary disease from their extracellular location in the lumen of the alveoli, and from their intracellular location in T2C or AM. External insults like smoke and pollution can disturb surfactant homeostasis and result in either surfactant insufficiency or accumulation. But disruption of surfactant homeostasis is also observed in many chronic adult diseases, including chronic obstructive pulmonary disease (COPD), and others. Sustained damage to the T2C is one of the postulated causes of idiopathic pulmonary fibrosis (IPF), and surfactant homeostasis is disrupted during fibrotic conditions. Similarly, surfactant homeostasis is impacted during acute respiratory distress syndrome (ARDS) and infections. Bioactive lipids like eicosanoids and sphingolipids also participate in chronic lung disease and in respiratory infections. We review the most recent knowledge on alveolar lipids and their essential metabolic and signaling functions during homeostasis and during some of the most commonly observed pulmonary diseases.

Keywords: Alveoli; COPD; IPF; Lipid metabolism; Lipids; Lungs; Pulmonary disease; Surfactant; Type 2 cells.

Fig. 1

Surfactant lipid synthesis and exocytosis. Simplified scheme of intracellular pathways leading to de novo synthesis of DPPC and its routing to lamellar bodies, from where it will be released into the alveolar lumen, where it will be used, recycled and degraded. For the synthesis, CDP-choline and diacylglycerol are coupled to form PC. A large proportion of PC is remodeled to render DPPC. Surfactant is stored in lamellar bodies until secretion to the alveolar lumen, where it organizes in bilayers and monolayers (see text for further detail). The surfactant life cycle is completed by its recycling by T2C or degradation by AM. T1C: type 1 cell; T2C: type 2 cell, AM: alveolar macrophage; LB: lamellar body; SP: surfactant protein; PC: phosphatidylcholine; DPPC: dipalmitoylphosphatidylcholine; CCTα: CTP:phosphocholine cytidylyltransferase alpha; PLA₂: phospholipase A2; LPCAT1: lysophosphatidylcholine acyltransferase 1.

Fig. 2

Alveolar lipids in pulmonary homeostasis. Schematic representation of alveolar cell types and the main lipids that partake in multiple functions during pulmonary homeostasis and pathophysiological conditions.