The Effects of Air Pollution Particles on Clearance Mechanisms Within the Lung

The effects of inhaled aIr pollution particles on lung clearance mechanisms is an important factor in understanding how the mammalian lung deals with such pollutants and, as such, how exposure to these pollutants can be regulated. The nanoparticle (diameter S lOOnm) and transition metal components of PMIO (particulate matter with a diameter less than lO~m) have been implicated as playing major roles in the impairment of alveolar macrophage function and the subsequent retention of particles in the respiratory system. The aim of this study was to investigate the effects of components of PMIO on macrophage functions both directly, by examining macrophage phagocytosis and migration, and indirectly, by studying peripheral factors affecting macrophage function such as recruitment by type II cells and complement based mechanisms. We hypothesised that the alveolar epithelial type II cell line would release leukocyte chemoattractants in response to particle exposure and that this could be measured by use of a macrophage migration assay. A sub-toxic dose (125 ~g/ml)of surrogate air pollution particles (fine and nanoparticle carbon black and titanium dioxide) was established by measuring LOH release from a murine alveolar macrophage cell line (1774.2) and an alveolar epithelial type II cell line (L-2) in response to particle exposure. Optimisation of a chemotaxis assay and measurement of macrophage migration towards conditioned medium obtained from the particle-exposed type II cells was conducted and it was determined that carbon black nanoparticles induced type II cells to secrete a chemoattractant that resulted in significant increases in macrophage migration compared to the negative control. This was in contrast to other particle types tested in this study which did not induce any increases in macrophage migration. It was also hypothesised that complement proteins could be involved in macrophage recruitment to sites of particle deposition and, as such, the migration of macrophages towards particle exposed blood serum was examined in vitro. Foetal bovine serum (FBS) was exposed to fine and nanoparticle caroon black and titanium dioxide (l-Smg/ml) for 2 hours. It was found, in accord with the previous study involving type II cells, that carbon black nanoparticles could activate the generation of chemotactic factors in serum that could subsequently induce significant increases (p