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.