Abstract
Background: Eosinophils are prominent in some patients with asthma and are increased in the submucosa in a subgroup of obese patients with asthma (OAs). Surfactant protein A (SP-A) modulates host responses to infectious and environmental insults. Objective: We sought to determine whether SP-A levels are altered in OAs compared with a control group and to determine the implications of these alterations in SP-A levels in asthmatic patients. Methods: Bronchoalveolar lavage fluid from 23 lean, 12 overweight, and 20 obese subjects were examined for SP-A. Mouse tracheal epithelial cells 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 lung parenchyma by means of immunostaining. Results: Significantly less SP-A (P =.002) was detected in samples from OAs compared with those from control subjects. A univariable regression model found SP-A levels were significantly negatively correlated with body mass index (r = −0.33, P =.014), whereas multivariable modeling demonstrated that the correlation depended both on asthma status (P =.017) and the interaction of asthma and body mass index (P =.008). Addition of exogenous TNF-α to mouse tracheal epithelial cells was sufficient to attenuate SP-A and eotaxin secretion. Allergen-challenged SP-A−/− mice that received SP-A therapy had significantly less tissue eosinophilia compared with mice receiving vehicle. Conclusions: SP-A functions as an important mediator in resolving tissue and lavage fluid eosinophilia in allergic mouse models. Decreased levels of SP-A in OAs, which could be due to increased local TNF-α levels, might lead to impaired eosinophil resolution and could contribute to the eosinophilic asthma phenotype.
Original language | English (US) |
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Pages (from-to) | 918-926.e3 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 141 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2018 |
Keywords
- IL-6
- Surfactant
- TNF-α
- asthma
- eosinophils
- eotaxin
- epithelial cells
- lung function
- obesity
- surfactant protein A
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology