C107-10 Lactoferrin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Targeting the Nadph Oxidase/Myeloperoxidase Axis: A Proteomic Insight Into Oxidative Stress Regulation

Rationale Oxidative stress, mediated by the NADPH oxidase and myeloperoxidase (MPO) axis, is a central mechanism in lipopolysaccharide (LPS)-induced acute lung injury (ALI). Although lactoferrin (LTF) has known anti-inflammatory properties, its direct role in regulating the core components of oxidative stress remains elusive. Methods A murine time-course model of LPS-induced ALI was established. Lung tissues were subjected to quantitative proteomic analysis. The resulting data were analyzed through an integrated bioinformatics approach, including principal component analysis (PCA), differential expression analysis, Short Time-series Expression Miner (STEM) trend analysis, and gene set enrichment analysis (GSEA). To functionally validate the proteomic findings, an in vivo intervention was conducted in mice using exogenous bovine lactoferrin (bLF), followed by assessments of histopathology, inflammatory cytokine levels, and key molecular markers of oxidative stress. Results Endogenous LTF expression peaked at day 1 post-LPS challenge, coinciding with maximal neutrophil infiltration. Proteomic and bioinformatic analyses consistently identified the neutrophil extracellular trap formation pathway as the most significantly enriched during the acute phase. Crucially, protein-protein interaction (PPI) network analysis revealed a direct interaction between LTF and MPO. Corroborating this finding, bLF treatment in mice significantly alleviated lung histopathological damage, reduced pro-inflammatory cytokine levels, and markedly suppressed the phosphorylation of the NADPH oxidase subunit p47 (p-p47) and MPO expression. Conclusion Our study demonstrates that LTF attenuates ALI by constituting a critical regulatory axis in oxidative stress, achieved through dually targeting NADPH oxidase activation and MPO function. These findings provide novel mechanistic insights into the protective role of LTF and underscore its therapeutic potential. This abstract is funded by: National Natural Science Foundation of China