Apoptotic damage during co-culture of lung epithelial cells and macrophages in the presence of metal nanoparticles is modulated by TNF-α from macrophages

Metal nanoparticles have attracted strong interest, because they open up a new field in fundamental science and have potential technological applications. The mechanisms of cytotoxic action as well as cellular target for metal nanoparticles remain to be elucidated. In the present study, the differences in the toxicity and cytokine production between mono- and co-culture with murine alveolar macrophages (RAW264.7) and alveolar epithelial cells (MLE12) in the presence of metal nanoparticles were elucidated. Among eight nanoparticles tested, n-Co, n-Cu, and n-Zn had higher degrees of cytotoxicity toward both cells than the other particles. These three metal nanoparticles induced a high degree of apoptotic damages, which, in turn, was correlated with extent of cytotoxicity at a lower concentration tested. In most cases, extent of apoptotic damage was higher with co-culture than with mono-culture for both cells due to a communication through TNF-α and other unknown factors between epithelial cells and macrophages. These results may be crucial in understanding the nanoparticle-induced apoptotic responses in the lung.