Toxicological Effects of Metal Oxide Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 177

modification of airway function (Humbles et al. 2004). Previous studies have shown
that exposure to ultrafine particles exerts strong adjuvant effect on the manifestation
of allergic airway inflammation (Alessandrini et al. 2006). A mouse model of aller-
gic airway inflammation was used to assess the potential health hazard of SiO 2 NPs
exposure in allergic airway disease.
This model was designed to induce a mild inflammatory response for evaluat-
ing potential enhancing effects of nanoparticle inhalation on the allergen-induced
inflammation of the lung. Allergen sensitization and challenge occurred as previ-
ously described (Alessandrini et al. 2006). Shortly, mice were sensitized by sev-
eral repetitive intraperitoneal injections of 1 μg ovalbumin/alum over 52 days and
sera were checked for specific immunoglobulins. Mice were then i.t. instilled with
SiO 2 naked, SiO 2 .PEG, SiO 2 .amino, or SiO 2 .phosphate at a concentration of 50 μg/
mouse, followed by ovalbumin aerosol challenge (20 min; 10 mg/ml). Five days later,
allergic inflammation was evaluated by cell differentiation of BALF, histology, lung
function analysis, and determination of cytokines/chemokines mRNA level in lung
tissue. BALF cell profiles from allergic phenotypes are characterized by an early
peak of neutrophils 24 h after allergen challenge and by a late increase in eosino-
phils, lymphocytes, and AM starting 48 h after allergen challenge.
In sensitized mice, intratracheal instillation of 50 μg SiO 2 .naked and SiO 2 .PEG
induced an increase in both lymphocytes, and to a higher extent of eosinophils in
the BALF. Lymphocytes were increased 2.8 fold and 3.4 fold by SiO 2 .naked and
SiO 2 .PEG, respectively, compared to respective controls (sensitized mice exposed
to nanoparticles supernatant). Eosinophils were increased 4.4 fold and 8.4 fold by
SiO 2 .naked and SiO 2 .PEG, respectively, compared to respective controls (sensi-
tized mice exposed to nanoparticles supernatant). The intratracheal instillation of
the same amount of SiO 2 .amino or SiO 2 .phosphate had no significant effect, either
on lymphocyte or on eosinophil recruitment in the BALF. In nonsensitized mice,
some effects on BALF cell recruitment following intratracheal instillation of all
nanoparticles tested were significant, but they were still significantly lower com-
pared to the corresponding effects on sensitized mice. Histological evaluation of
lung tissue showed that epithelial mucus cell hyperplasia was increased in lungs of
sensitized mice instilled with SiO 2 .naked and SiO 2 .PEG prior to allergen challenge
compared to sensitized mice instilled with respective supernatant prior to allergen
challenge.
Airway hyperresponsiveness was also compromised in mice exposed to SiO 2 .
naked and SiO 2 .PEG: Following a standard protocol of methacholine provocation,
airway resistance was significantly increased in mice instilled with SiO 2 .PEG and
dynamic compliance was significantly reduced in mice instilled with SiO 2 .naked.
No significant effects on lung function were evaluated in sensitized mice exposed to
SiO 2 .amino or to SiO 2 .phosphate prior to allergen challenge.
Evaluation of both Th1 and Th2 cytokines and eosinophil activation markers in
the lungs of sensitized mice showed that SiO 2 .naked and SiO 2 .PEG NPs induced a
significant increase in the expression of IL-13, a cytokine which plays an impor-
tant role in airway hyperreactivity and eosinophilia (Wills-Karp and Chiaramonte
2003), but no alteration of Th1 cytokines. In addition, both nanoparticles induced a
significant expression of Ear11, an important eosinophil activation marker in asthma