Ambient Ultrafine Particles Promote Allergic Airway Inflammation by Increasing T-helper 2 (Th2) and T-helper 17 (Th17) Gene Expression during the Recall Immune Response

Ning Li (1,2), Jack Harkema (1,3), Ryan Lewandowski (3), Meiying Wang (1,2), Lori Bramble (3), Glenn Gookin (4), Michael Kleinman (1,4), Constantinos Sioutas (1,5), Andre Nel (1,2)

(1) Southern California Particle Center (2) University of California Los Angeles (3) Michigan State University (4) University of California Irvine (5) University of Southern California

     Abstract Number: 209
     Last modified: November 8, 2009

Abstract

Background: Ambient particulate matter (PM) exposure is a contributing factor for increased respiratory morbidity and mortality in urban environment including asthma. Accumulating evidence has suggested that increased prevalence of allergic disease may be related to the effect of PM on the immune system. Recently, we have demonstrated that ambient pro-oxidative ultrafine particles (UFP) could act as an adjuvant for allergic sensitization in a mouse model using intranasal instillation. This adjuvant effect could also be used to study the recall immune response and may explain asthma exacerbation in atopic individuals after a sudden surge in ambient PM levels.

Objective: To determine whether inhalation exposure to ambient UFP near an urban freeway could further enhance allergic inflammation in already sensitized animals.

Methods: Balb/c mice were sensitized with saline, ovalbumin (OVA), or OVA plus UFP and exposed to filtered air or ambient UFP during OVA challenge in a mobile animal research laboratory near a major freeway in downtown Los Angeles. OVA-specific antibody production, allergic airway inflammation and cytokine/chemokine production in the lung were studied.

Results: Ambient UFP exposure on as few as five occasions was highly effective in boosting the OVA recall immune response in sensitized animals, including generation of allergic inflammation in distal and terminal airways and increased production of OVA-specific antibodies. The enhanced secondary immune response was characterized by Th2 and Th17 cytokine profiles in the lung.

Conclusion: Pro-oxidative ambient UFP provide a put in boosting the secondary immune response to an experimental allergen, underlining the importance of vehicular traffic on the exacerbation of allergic airway inflammation. This may contribute to asthma flares in atopic subjects in an urban setting and might require lower exposure levels than previously suspected.