Anti-Oxidant Taurine Treatment Reduces Pulmonary Inflammation Induced by Allergen and Diesel Particulate Matter Challenge in a Mouse Model of Asthma
J Kim, F Chiem, S Natarajan, L Vaickus, D Remick. Boston University, Boston, MA
Background: Many studies show a link between ambient particulate air pollution and exacerbation of pre-existing pulmonary diseases such as asthma. Air pollutants, including diesel particulate matter (DPM), exerts exogenous oxidative stress on biological systems exacerbating lung injury and inflammation in animals and humans. We investigated the pathophysiologic pathways and mediators responsible for exacerbation of asthma-like pulmonary inflammation and airway hyperresponsiveness (AHR) by DPM suspension in a mouse model of asthma and subsequent alleviation of asthma-like symptoms by the anti-oxidant, taurine.
Design: A house dust sample containing high concentrations of cockroach allergens and endotoxin was used for this study. BALB/c mice were exposed to 3 pulmonary challenges via hypopharyngeal administration of the house dust extract (HDE) on day 0, 14 and day 21. Groups of mice received DPM or PBS, 1 hr before each allergen challenge. On day 22, bronchoalveolar lavage (BAL) fluid was collected for cells and cytokines, with AHR measured prior to sacrifice. Whole lungs were collected for myeloperoxidase assay (MPO). For taurine treatment, groups of mice received taurine or the inactive analog alanine following DPM and HDE challenge as describe above.
Results: Compared to vehicle, DPM significantly increased the airway infiltration of eosinophils (225905162 vs 7419215693, p 0.0049), lymphocytes (399666091 vs 7252213814, p 0.042), and neutrophils (30785029270 vs 51331480458, p 0.025). MPO (94.512.4 vs 192.39.2, p 0.0001) and AHR (0.500.05 vs 5.501.70, p 0.0011) in DPM treated mice were also substantially elevated compared to the vehicle group. Pulmonary expression of chemokines and cytokines were significantly increased by DPM challenge. Histological examination of the lung demonstrated a substantial increase of mucus production in airway by DPM challenge. The anti-oxidant taurine significantly reduced AHR (6.050.1 vs 2.740.17, p 0.001) as well as pulmonary infiltration of neutrophils (395005383 vs 191005360, p 0.05) and eosinophils (201458598 vs 88603372, p 0.05) in the allergen plus DPM model.
Conclusions: These results demonstrate that intratracheal administration of DPM exacerbates asthma-like pulmonary inflammation. Treatment with the anti-oxidant taurine significantly reduces the pulmonary inflammation in a mouse model of asthma, suggesting that oxidant stress may be an important component of the asthmatic response.
Monday, March 9, 2009 1:00 PM
Poster Session II # 234, Monday Afternoon