Comparative Ligandomic Analysis of Human Lung Epithelial Cells Exposed to PM_2.5

Objective: To investigate whether exposure to particulate matter of diameter equal to or less than 2.5 μm (PM_2.5) alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface ligands and quantifying their binding activity. Methods: Human A549 lung epithelial cells (LECs) were treated with or without PM_2.5. Ligandomic profiling was applied to these cells for the global identification of LEC-binding ligands with simultaneous quantification of binding activity. Quantitative comparisons of the entire ligandome profiles systematically identified ligands with increased or decreased binding to PM_2.5-treated LECs. Results: We found 143 ligands with increased binding to PM_2.5-treated LECs and 404 ligands with decreased binding. Many other ligands showed no change in binding activity. For example, apolipoprotein E (ApoE), Notch2, and growth arrest-specific 6 (Gas6) represent ligands with increased, decreased, or unchanged binding activity, respectively. Both ApoE and Gas6 are phagocytosis ligands, suggesting that phagocytic receptors on LECs after stimulation with PM_2.5 were differentially upregulated by PM_2.5. Conclusion: These results suggest that the newly-developed ligandomics is a valuable approach to globally profile the response of LECs to PM_2.5 in terms of regulating the expression of cell surface receptors, as quantified by ligand binding activity. This quantitative ligandome profiling will provide indepth understanding of the LEC molecular response on the cell surface to particulate matter air pollution.