Human Toxicology and Effects of Nanoparticles - Environmental and Human Health Impacts of Nanotechnology - page 362

then triggers the polymerisation and rearrangement of the actin cytoskeleton to
form membrane extensions, so that the plasma membrane surrounds the material
to be internalised (Liu and Shapiro 2003; Perret et al. , 2005 ; Khalil et al. , 2006 ). The
phagosome that is formed will fuse with lysosomes, so that the cargo can be
degraded if possible (Perret et al. 2005 ).
As described in the introduction, macrophages play a key role in the defence of
the respiratory system. However, such mechanisms are not unique to the lung.
Infl ammatory cells such as macrophages can penetrate almost all tissues of the
body, providing a useful defence mechanism against inhaled, ingested, injected,
implanted and dermally absorbed particles.
Some studies suggest that relatively low concentrations of TiO 2 and carbon black
nanoparticles increase the phagocytic ability of macrophages (Renwick et al. , 2001 ;
Hoet and Nemery, 2001), while at higher concentrations the phagocytic function of
these cells is diminished (Renwick et al. , 2001 ; Lundborg et al. , 2006 ). The mecha-
nism or cause of this inhibition remains unknown. Macrophages have the ability to
ingest large volumes of particles and, therefore, inhibition of phagocytosis could be
as a result of fi lling of the cell volume or a decrease in membrane area to allow
continued uptake. One research group has suggested that nanoparticle uptake cells
does not require membrane invagination, phagocytosis or pinocytosis (Geiser et
al. , 2005), suggesting uptake via diffusion across the cell membrane. Further studies
are required to verify this result with other types of nanoparticles and other cell
types.
Epithelial cells also play an important role in defence by providing a barrier
across which particles must pass to gain access to the body. As mentioned previ-
ously, carbon black nanoparticles induce glutathione depletion, indicative of oxida-
tive stress, in a human lung epithelial cell line (Stone et al. , 1998 ). Epithelial cells
when exposed to damaging or infective agents can generate chemotactic factors;
these chemotactic factors stimulate infl ammatory cell recruitment and, therefore,
infl ammation. For example, some nanoparticles have been shown in vitro to stimu-
late production of the chemoattractant interleukin-8 by epithelial cells (Montellier
et al. , 2006 ).
As mentioned previously, carbon black, TiO 2 and polystyrene beads are all low
solubility materials. It is also very important to note that they are also relatively
low toxicity materials. For newly engineered nanoparticles made from more toxic
materials (e.g. the cadmium used in some quantum dots) and biodegradable materi-
als (e.g. the polymers used in drug delivery), the toxicity may be very different.
Therefore, new studies will have to focus on whether the nanoparticulate nature
of these materials impacts upon, or interacts with their chemical mechanism of
action resulting in any altered or unexpected toxicity.

9.2.6 Nanoparticle Interactions with Other Pollutants and Molecules

Due to the presence of transition metals in particulate air pollution, Wilson et al.
(2002) investigated the effect of mixing carbon nanoparticles with metal salts.
Transition metals such as iron are known to generate hydroxyl radicals via Fenton
chemistry (Stohs and Bagchi, 1995), and since 14 nm carbon black particles have