Pulmonary surfactant protein SP-C regulates lipid vesicle uptake by alveolar type II cells and macrophages: Role of lipids, palmitoylation, and environment

Abstract

Pulmonary surfactant protein C (SP-C) may play a key role in alveolar homeostasis by modulating vesicle uptake in alveolar cells. This study explores how SP-C regulates internalization of model unilamellar lipid vesicles by type II alveolar epithelial cells (AECII) and alveolar macrophages (AMϕ), focusing on the effect of lipid composition, palmitoylation state, and interactions with external stimuli like lipopolysaccharides (LPS) or the other hydrophobic surfactant protein SP-B. Using fluorescence-based techniques, we demonstrated that SP-C enhances vesicle uptake in a lipid-dependent manner. While AECII internalize vesicles regardless of lipid composition, AMϕ show a preference for vesicles with specific lipid profiles. The palmitoylation of SP-C is essential for efficient vesicle uptake, highlighting the importance of membrane-protein interactions in this process. Furthermore, SP-C colocalizes with acidic organelles within both cell types, suggesting its involvement in intracellular trafficking and surfactant homeostasis. Notably, SP-C facilitates LPS uptake by AMϕ, potentially contributing to immune modulation in the alveolar spaces. The contribution of SP-C to metabolism and pulmonary immunity has important implications in lung diseases involving surfactant dysfunction or immune dysregulation.