BackgroundInhalation of lead oxide nanoparticles (PbO NPs), which are emitted to the environment by high-temperature technological processes, heavily impairs target organs. These nanoparticles pass through the lung barrier and are distributed via the blood into secondary target organs, where they cause numerous pathological alterations. Here, we studied in detail, macrophages as specialized cells involved in the innate and adaptive immune response in selected target organs to unravel their potential involvement in reaction to subchronic PbO NP inhalation. In this context, we also tackled possible alterations in lipid uptake in the lungs and liver, which is usually associated with foamy macrophage formation. MethodsFemale mice CD-1 (ICR), as a model organism, were placed into whole-body inhalation chambers and continuously exposed to PbO NPs at a concentration of 0.956 × 106 NPs/cm3 for 11 weeks (24/7). At the end of the exposure period, target organs (lung, liver, kidney, and spleen) were collected for analyses.ResultsThe histopathological analysis of PbO NP exposed lung revealed serious chronic inflammation of lung tissues. The number of foamy macrophages was significantly increased in lung, and they contained numerous cholesterol crystals. PbO NP inhalation induced changes in expression of phospholipases C (PLC) as enzymes linked to macrophage-mediated inflammation in lungs. In the liver, the subchronic inhalation of PbO NPs caused predominantly hyperemia, microsteatosis or remodeling of the liver parenchyma, and the number of liver macrophages was also significantly increased. The expression of a scavenger receptor CD36 and transporter ABCA1, which are associated with lipid metabolism, was significantly altered in the liver. No microscopic or serious functional kidney alterations were detected after subchronic PbO NP exposure and CD68 positive cells were present in the physiological mode in the interstitial tissues. ConclusionOur study determined the association of increased cholesterol and lipid storage in targeted tissues with the alteration of scavenger receptors and phospholipases C after subchronic inhalation of PbO NPs and uncovered processes, which contribute to steatosis in liver and foamy macrophages in lungs.