  Metallic nanoparticles are more and more widely used in an increasing number
of applications. Consequently, they are more and more present in the
environment, and the risk that they may represent for human health must be
evaluated. This requires to increase our knowledge of the cellular responses to
nanoparticles. In this context, macrophages appear as an attractive system.
They play a major role in eliminating foreign matter, e.g. pathogens or
infectious agents, by phagocytosis and inflammatory responses, and are thus
highly likely to react to nanoparticles. We have decided to study their
responses to nanoparticles by a combination of classical and wide-scope
approaches such as proteomics. The long term goal of this study is the better
understanding of the responses of macrophages to nanoparticles, and thus to
help to assess their possible impact on human health. We chose as a model
system bone marrow-derived macrophages and studied the effect of commonly used
nanoparticles such as TiO2 and Cu. Classical responses of macrophage were
characterized and proteomic approaches based on 2D gels of whole cell extracts
were used. Preliminary proteomic data resulting from whole cell extracts showed
different effects for TiO2-NPs and Cu-NPs. Modifications of the expression of
several proteins involved in different pathways such as, for example, signal
transduction, endosome-lysosome pathway, Krebs cycle, oxidative stress response
have been underscored. These first results validate our proteomics approach and
open a new wide field of investigation for NPs impact on macrophages
