Abstract
BackgroundAlthough major concerns exist regarding the potential consequences of human exposure to nanoparticles (NP), no human toxicological data is currently available. To address this issue, we took welders, who present various adverse respiratory outcomes, as a model population of occupational exposure to NP.The aim of this study was to evaluate if welding fume-issued NP could be responsible, at least partially, in the lung alterations observed in welders.MethodsA combination of imaging and material science techniques including ((scanning) transmission electron microscopy ((S)TEM), energy dispersive X-ray (EDX), and X-ray microfluorescence (μXRF)), was used to characterize NP content in lung tissue from 21 welders and 21 matched control patients. Representative NP were synthesized, and their effects on macrophage inflammatory secretome and migration were evaluated, together with the effect of this macrophage inflammatory secretome on human lung primary fibroblasts differentiation.ResultsWelding-related NP (Fe, Mn, Cr oxides essentially) were identified in lung tissue sections from welders, in macrophages present in the alveolar lumen and in fibrous regions. In vitro macrophage exposure to representative NP (Fe2O3, Fe3O4, MnFe2O4 and CrOOH) induced the production of a pro-inflammatory secretome (increased production of CXCL-8, IL-1ß, TNF-α, CCL-2, −3, −4, and to a lesser extent IL-6, CCL-7 and −22), and all but Fe3O4 NP induce an increased migration of macrophages (Boyden chamber). There was no effect of NP-exposed macrophage secretome on human primary lung fibroblasts differentiation.ConclusionsAltogether, the data reported here strongly suggest that welding-related NP could be responsible, at least in part, for the pulmonary inflammation observed in welders. These results provide therefore the first evidence of a link between human exposure to NP and long-term pulmonary effects.
Highlights
Major concerns exist regarding the potential consequences of human exposure to nanoparticles (NP), no human toxicological data is currently available
CD68 staining revealed the presence of a higher number of macrophages in lung tissue sections from welders as compared to control patients, localized in the alveolar lumen as well as in the fibrous tissue (Figure 1)
Effect of macrophage secretome on human lung pulmonary fibroblast activation Since lung from welders contained an increased number of macrophages in alveolar lumen and in areas of fibrosis, and since NP induced an inflammatory secretome in macrophages in vitro that can be detected in situ in macrophages localized in the same areas, we investigated the effects of macrophage secretome on fibroblasts to myofibroblasts differentiation and fibroblasts proliferation
Summary
Major concerns exist regarding the potential consequences of human exposure to nanoparticles (NP), no human toxicological data is currently available To address this issue, we took welders, who present various adverse respiratory outcomes, as a model population of occupational exposure to NP. Nanotechnologies represent a major stake of the 21rst century They are aimed at conceiving, characterizing and producing materials at the scale of the billionth meter; the nanometer. This point is critical since human exposure studies constitute the cornerstone of risk evaluation for health after (chronic) exposure to environmental agents, especially in the occupational context During their everyday occupation, welders are exposed to a complex aerosol of gases (e.g. carbon monoxide, ozone), and hazardous metal fumes composed of chain-like agglomerates of particles, with a primary size in the nanometer size range [9].
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