Figure 2.
Roles of native and oxidized surfactant glycerophospholipids in inflammatory lung responses to the environment. The complex immune interactions that occur in the alveolus between native surfactant glycerophospholipids (PLs) and environmental agents are depicted. Surfactant PLs, including dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and 1-palmitoyl-2-arachidonoyl-phosphatidylcholine (PAPC) are synthesized by alveolar epithelial type 2 cells and released as lamellar bodies that unravel to form the surfactant layer. Various lipids are depicted in the surfactant monolayer inset, but native surfactant is DPPC predominant. Inhaled agents and reactive oxygen species (ROS) derived from host cells oxidize PAPC and PE into oxidized PLs (oxPLs), as shown. Native PLs antagonize delivery of pathogens and pathogen-associated molecules to cellular receptors, and oxPL species act on multiple receptors on alveolar macrophages, both promoting and suppressing inflammation. Plasma lipoproteins, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very LDL (VLDL), deliver and receive lipids to/from alveolar epithelial cells, influencing PL synthesis. ABCA1, ATP binding cassette A1 transporter; CCT, cytidyltransferase; EP2, prostaglandin E2 receptor; IAV, influenza A virus; KETE, 15-ketoeicosatetraenoic acid; MALP-2, macrophage-activating lipopeptide-2; MARCO, macrophage receptor with collagenous structure; Nrf2, nuclear factor E2-related factor 2; oxPAPC, oxidized PAPC; PEIPC, 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine; PPAR, peroxisome proliferator-activated receptor; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SR-BI, scavenger receptor class B member I; TGF, transforming growth factor; TLR, Toll-like receptor.