A clearance period after soluble lead nanoparticle inhalation did not ameliorate the negative effects on target tissues due to decreased immune response

Abstract Background: The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO 3 ) 2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. Mice were exposed to Pb(NO 3 ) 2 NPs in whole-body inhalation chambers for up to 11 weeks. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs (lung, liver, kidney, spleen, bone and blood). Results: After exposure to Pb(NO 3 ) 2 NPs, the lead concentration was the highest in femur at all designated time points with the exception of 3-day inhalation. In contrast to other organs, the ability to clear the lead from the femur was very low. In the lungs, Pb(NO 3 ) 2 NP inhalation induced serious structural changes; lung damage was present even after a 5-week clearance period despite the lead being almost completely eliminated from the lung tissue. Furthermore, in secondary target organs (kidney and liver), Pb(NO 3 ) 2 NPs induced several morphological defects, with alterations that remained visible after the clearance period even though the tissue lead concentrations decreased to minimal values. The numbers of lung and liver macrophages were significantly decreased after 11-week Pb(NO 3 ) 2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, was increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines (tumour necrosis factor alpha [TNF-α], transforming growth factor beta 1 [TGFβ1], interleukin 6 [IL-6], IL-1α and IL-1β) displayed a tissue-specific response to lead exposure. Conclusions: Taken together, diminished inflammatory response in lung and liver after Pb(NO 3 ) 2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by enhanced pathological changes in target organs, even after a 5-week clearance period.