ToxSci Advance Access originally published online on July 13, 2005
Toxicological Sciences 2005 87(2):409-418; doi:10.1093/toxsci/kfi255
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Ultrafine Carbon Black Particles Cause Early Airway Inflammation and Have Adjuvant Activity in a Mouse Allergic Airway Disease Model
Department of Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht University, 3584 CM Utrecht, The Netherlands
Received June 13, 2005; accepted July 15, 2005
To gain more insight into the mechanisms of particulate matter (PM)-induced adjuvant activity, we studied the kinetics of airway toxicity/inflammation and allergic sensitization to ovalbumin (OVA) in response to ultrafine carbon black particles (CBP). Mice were exposed intranasally to OVA alone or in combination with different concentrations of CBP. Airway toxicity and inflammation were assessed at days 4 and 8. Immune adjuvant effects were studied in the lung draining peribronchial lymph nodes (PBLN) at day 8. Antigen-specific IgE was measured at days 21 and 28, whereas allergic airway inflammation was studied after OVA challenges (day 28). Results show that a total dose of 200 µg CBP per mouse, but not 20 µg or 2 µg, induced immediate airway inflammation. This 200 µg CBP was the only dose that had immune adjuvant activity, by inducing enlargement of the PBLN and increasing OVA-specific production of Th2 cytokines (IL-4, IL-5, and IL-10). The immune adjuvant activity of 200 µg CBP dosing was further examined. Whereas increased OVA-specific IgE levels in serum on day 21 confirms systemic sensitization, this was further supported by allergic airway inflammation after challenges with OVA. Our data show a link between early airway toxicity and adjuvant effects of CBP. In addition, results indicate that local cytokine production early after exposure to CBP is predictive of allergic airway inflammation. In addition this model appears suitable for studying the role of airway toxicity, inflammation and other mechanisms of particle adjuvant activity, and predicting the adjuvant potential of different particles.
Key Words: ultrafine particles; adjuvant; allergy; intranasal; inflammation.
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