Summary

Nanotechnologies have a tremendous potential for use in a variety of industries, and there are significant financial gains to be made. As in other Canadian provinces and many industrialized countries, a growing number of Québec companies are producing nanomaterials and nanoparticles (NP), not to mention those introducing more and more NPs in their products. The number of Québec workers employed in the manufacture and synthesis of NPs will increase in the years ahead. In addition, the number of workers who will be required to handle and process NPs in nanotechnology fields in general will continue to grow as well. In other words, we can expect the enthusiasm for nanotechnologies to grow not only the number of workers exposed to NPs but the exposure of the general public given that thousands of products used in everyday life already contain NPs. The dynamic, rich and growing literature in the field clearly demonstrates that exposure to NPs entails health risks. Though this research identifies a number of NP exposure hazards (cytotoxic and genotoxic effects, oxidative stress, cancers, etc.), inflammation remains one of the most frequently reported harmful effect.

Inflammation is a completely normal biological response, to infection for example, that resolves on its own when good health returns. Uncontrolled inflammation, however, can lead to disease and immune system disorders, such as asthma, allergies and arthritis, to name a few. In fact, practically all human diseases have an inflammatory component at one stage in their development. The inflammatory response is complex and involves a number of mediators and cells, among them leukocytes (white blood cells). Neutrophils (NT) and eosinophils (EO) are white blood cells known to play a major role in inflammation. Because NPs are so small, they are highly likely to be inhaled when present in any setting, leading to inflammatory lung diseases in workers or exacerbation of existing disorders. In fact, a number of in vivo studies of animals exposed to NPs demonstrate increased presence of NTs or EOs in bronchoalveolar washings and in the lungs. In addition, with NPs now found in a growing variety of everyday household products, exposure is possible via routes other than inhalation, including skin contact and even ingestion. It is inevitable then that NPs will eventually work their way into the blood stream or through different tissues and interact directly with NTs or EOs.

Recent research also clearly shows that NPs have the ability to alter NT and EO biology. Though a number of NPs have inflammatory properties in vitro, there are no data on sex-dependent differences in inflammatory effects of NPs in humans, unlike in a few animal studies. Our study was designed to fill that gap and expand our knowledge in this field. NTs and EOs from blood samples obtained from healthy consenting men and women were treated in vitro with different NPs to which Québec workers risk exposure to assess the modulating capabilities of functions connected with the inflammatory process. Among the functions investigated were the ability of NPs to affect apoptosis, production of reactive oxygen species (ROS), phagocytosis, production of certain cytokines and NT/EO adhesion and migration. With this experimental approach, we were able to show sex-differentiated effects of NPs on NT and EO biology. Study data and observations as a whole demonstrate certain differences between the sexes. However, no major trends in opposite directions were noted: for example, NPs will not trigger a response in male NTs/EOs but inhibit or reverse it in female NTs/EOs. In general, if an NP enhanced or diminished a function or response, result analysis considering donor sex showed cells from female blood samples were preferentially more affected. Though this was at the cellular level rather that throughout the body as a whole, NPs do seem to have a greater impact on female cells. This correlates well with the sex dimorphism noted in the human immune system; that is, women have more intense immunological responses.

The contributions of this study of isolated cells from healthy individuals are multiple, including acquisition of new information that may help advance our knowledge of NP health effects. The study results and findings, together with those described by other teams studying different aspects of NP toxicity, will also help in making decisions about occupational NP exposure risk management. Besides increasing our knowledge of the mechanisms of action and biological effects of NPs in connection with inflammation and building a highly qualified team specializing in this research area, the experimental approach developed in this study demonstrating that NTs and EOs can react differently depending on sex will help in making the best use of NPs in different therapeutic strategies and furthering the shift to personalized medicine. Also, this study can definitely serve as a starting point for improving regulatory procedures to ensure safe use of NPs in the workplace. In the longer term, the results of this study of isolated cells of healthy individuals who are not workers or individuals potentially or voluntarily exposed to NPs could help in deciding about using blood cells from workers targeted based on NP exposure (with donor consent) to study NT or EO functions that might have disproportionate sex-dependent functional responses.