BPS2026 – Compositional and structural factors modulate surfactant protein SP-C-mediated lipid vesicle uptake by alveolar cells

Pulmonary surfactant protein C (SP-C) plays a critical role in maintaining alveolar homeostasis by influencing vesicle uptake by alveolar cells. This study investigates how SP-C regulates the internalization of model lipid vesicles by two key cell types in the alveolar space: type II alveolar epithelial cells (AECII) and alveolar macrophages (AMϕ). We examined the effects of vesicle lipid composition, the palmitoylation state of SP-C, and interactions with external stimuli such as lipopolysaccharides (LPS) or the hydrophobic surfactant protein SP-B. Using fluorescence-based assays, we found that SP-C enhances vesicle uptake in a lipid-dependent manner. While AECII internalize vesicles regardless of lipid composition, AMϕ preferentially internalize vesicles with specific lipid profiles. Palmitoylation of SP-C is essential for efficient uptake, underscoring the importance of protein-membrane interactions. Moreover, SP-C colocalizes with acidic organelles in both cell types, suggesting a role in intracellular trafficking and surfactant turnover. Notably, SP-C also promotes LPS uptake by AMϕ, pointing to a potential role of this surfactant protein in immune modulation within the alveolar microenvironment. Overall, our findings highlight the dual role of SP-C in surfactant metabolism and pulmonary immunity, with important implications for lung diseases involving surfactant dysfunction or immune dysregulation.