Acute co-exposure to urban particulate matter and aircraft noise elicits lung-centered immune-redox proteomic remodeling in mice.

Particulate air pollution and transportation noise frequently co-occur, but their combined molecular effects are poorly defined. We used data-independent acquisition (DIA) LC-MS/MS proteomics to profile lung, brain, and heart from male C57BL/6J mice exposed for 3 days to NIST SRM 1648a urban particulate matter (PM), aircraft noise (NOISE), PM + NOISE, or control conditions. The exposure model is the acute co-exposure paradigm previously characterised with orthogonal functional, redox, and inflammatory endpoints by Kuntic et al. The lung was the dominant responsive organ. PM + NOISE produced the broadest pulmonary response and the strongest induction of immune and macrophage-associated proteins, including acute-phase, particle-handling, interferon-linked, and phagosome-associated markers. This immune signal was accompanied by NADPH oxidase and iron-handling components, altered epithelial barrier markers, and endothelial and extracellular-matrix perturbation. The principal pulmonary modules agreed with orthogonal endpoints previously measured in the parent exposure experiment, including pulmonary NOX-2 and HO-1 protein, in situ reactive oxygen species formation, Cd68 and Mcp-1 transcripts, circulating cytokines, increased systolic blood pressure, impaired endothelium-dependent relaxation of the aorta, and cerebral and retinal arteriolar microvascular dysfunction. Brain and heart responses were lower in amplitude and involved selective redox, neuronal, contractile, metabolic and matrix-associated programs. Observed-versus-expected analyses showed that most stress-responsive proteins scaled proportionally, whereas a smaller set enriched for ribosome, RNA-processing, and chromatin functions was constrained. Integration with transcriptomic data showed strong mRNA-protein concordance in lung and greater transcript-protein divergence in brain and heart. Acute co-exposure therefore increases early pulmonary immune-redox burden without uniform additive escalation across molecular systems.