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Impaired Tissue Eosinophil Resolution in Obese Asthma May Be Due to Surfactant Protein-A Insufficiency.
Monday, March 6, 2017: 2:15 PM
Rooms B303-B304 (Georgia World Congress Center, Building B)
Julie Ledford, PhD, , , ,
Rationale: Eosinophils are prominent in individuals with type 2-driven asthma and submucosal eosinophils are elevated in a subgroup of obese asthmatics. Surfactant protein-A (SP-A) is a secreted lipoprotein complex that has recently been shown to mediate several eosinophil activities. We hypothesized that obese asthmatics may have enhanced tissue eosinophilia due to decreased SP-A in the airway.

Methods: Bronchoalveolar lavage fluid from 23 lean (13 normal, 10 asthma) and 20 obese (9 normal, 11 asthma) subjects were examined for SP-A. Mouse tracheal epithelial cells (MTECs) grown at an air-liquid interface were used for mechanistic studies. SP-A-/- mice were challenged in allergen models and exogenous SP-A therapy was given after the last challenge. Eosinophils were visualized and quantitated in the lung parenchyma by immunostaining for mouse eosinophil major basic protein. 

Results: Significantly less SP-A was detected in samples from obese asthmatics compared to lean asthmatics. SP-A levels negatively correlated with BMI and positively correlated with lung function. Allergic SP-A-/- mice that received SP-A therapy had significantly less tissue eosinophilia compared to mice receiving vehicle. In vitro studies revealed that SP-A deficient epithelial cells have attenuated eotaxin production under basal conditions.

Conclusions: SP-A functions as an important mediator in resolving tissue eosinophilia. Therefore, significantly decreased levels of SP-A in obese asthmatics could contribute to asthma exacerbations.