The increasing use
of multiwalled carbon nanotubes (MWCNTs) could
increase the risk of allergic lung disease in occupational or consumer
settings. We previously reported that MWCNTs exacerbated allergic
lung disease in mice induced by extract from house dust mites (HDM),
a common cause of asthma in humans. Because MWCNTs avidly bind biomolecules
to form protein coronas that can modify immunotoxicity, we hypothesized
that exacerbation of allergic lung disease in mice caused by coexposure
to MWCNTs and HDM extract was due to the formation of an allergen
corona. In a first set of experiments, male and female C57BL/6J mice
were coexposed to MWCNTs and HDM extract over 3 weeks compared to
MWCNTs or HDM extract alone. In a second set of experiments, mice
were exposed to pristine MWCNTs or MWCNTs with an HDM allergen corona
(HDM-MWCNTs). HDM-MWCNTs were formed by incubating MWCNTs with HDM
extract, where ∼7% of proteins adsorbed to MWCNTs, including
Der p 1 and Der p 2. At necropsy, bronchoalveolar lavage fluid was
collected from lungs to assess lactate dehydrogenase, total protein
and inflammatory cells, while lung tissue was used for histopathology,
qPCR, and Western blotting. Compared to MWCNTs or HDM extract alone,
coexposure to MWCNTs and HDM extract or exposure to HDM-MWCNTs increased
pathological outcomes associated with allergic lung disease (eosinophilia,
fibrosis, mucous cell metaplasia), increased mRNAs associated with
fibrosis (
Col1A1
,
Arg1
) and enhanced
STAT6 phosphorylation in lung tissue. These findings indicated that
exacerbation of HDM-induced allergic lung disease by MWCNTs is due
to an allergen corona.