Gunshot residue PM2.5 exposure: Cardiopulmonary effects and the role of RAGE signaling in inflammation and oxidative stress.

Gunshot residue (GSR) is an airborne mixture of chemicals and particles released after firearm discharge. There is limited information on cardiopulmonary effects of GSR specifically in a health relevant size fraction. This study evaluates the acute cardiopulmonary effects of GSR (particles ≤2.5 µm; GSR PM2.5) and investigates the role of the receptor for advanced glycation end-products (RAGE) signaling cascade in the mediation of inflammation and oxidative stress using wild-type (WT) and RAGE knockout (RKO) mice. GSR PM2.5 collected during a law enforcement pistol training contained characteristic GSR markers (lead, copper, and 2,4- dinitrotoluene). Right ventricle measurements were lower in the GSR PM2.5 treated animals compared to the control indicating potential pulmonary vasodilation regardless of genotype. Lead content in the heart was significantly higher in the GSR PM2.5 exposed mice, indicating systemic circulation. Inflammatory markers (NF-κB, TNF-α, SOD-1 and 2) in the lungs of RKO animals were significantly lower compared to the WT groups. The cardiovascular effects, differential inflammatory expression, and influence of RAGE signaling pathway on the cardiorespiratory response to GSR PM2.5 highlight the need for further investigation of longer exposure durations, mechanistic influences, and a more extensive chemical characterization of GSR PM2.5 in toxicological assessments.