Airway region-specific effects of Carbon Black nanoparticles

Introduction:

Carbon Black nanoparticles (CBNPs), less than 100nm in size, are present in industrially produced carbon black mainly used for reinforcement of elastomers (e.g. in tyres) but also for paints, varnishes, toner and batteries. Upon inhalation CBNPs may have toxicological and inflammatory effects on the lung such as epithelial cell death or proliferation, persistent inflammation, fibrosis and even lung cancer. The effects of CBNPs could be mediated by oxidative stress, pro-inflammatory and pro-fibrotic cytokines and/or expression of genes responsible for cell proliferation. The commercially available CBNPs Printex 90 (P90) and the quartz DQ12 are well described particles possessing cytotoxicological and pro-inflammatory properties in mice and epithelial cell lines. We sought to investigate if these CBNPs exert similar effects in mouse airway explants and if such effects were different in distal versus proximal airways.

Methods:

The impact of CBNPs on different airway regions was assessed by microdissection of proximal and distal airways from mouse lungs and ex vivo stimulation. To isolate proximal and distal airways the parenchyma was removed. Airways were cultured on transwell inserts via an air-liquid interface (ALI) culture method. Cytotoxicity was assessed by LDH release and cytokine mRNA expression by quantitative real-time PCR.

Results:

In contrast to previous findings in mice and epithelial cell culture our preliminary results could not show pro-inflammatory effects of P90 or DQ12 on microdissected airways by analyzing the synthesis of cytokines like IL-1 beta and KC mRNA within 6 hours after stimulation. However, there was a slight indication that IL-6 expression was upregulated when proximal airways were incubated with either DQ12 or P90. Incubation with P90 or DQ12 did not result in increased cytotoxicity in distal and proximal airways which is also different from previous findings in cell culture.

Conclusion/Outlook:

Although our results do not show significant cytotoxic or pro-inflammatory effects of P90 and DQ12 on proximal and distal airways, this does not exclude that oxidative stress, apoptosis or proliferation of airway cells are affected by CBNP. In the future, chemically modified CBNPs will be analysed to reveal the impact of functional surface groups on the particles toxicological properties.

Suppported by the BMBF (FKZ 03X0093A).