Obese asthmatic patients have decreased surfactant protein A levels: Mechanisms and implications - 07/03/18
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.
Le texte complet de cet article est disponible en PDF.Key Words : Surfactant, surfactant protein A, obesity, asthma, eosinophils, TNF-α, eotaxin, IL-6, epithelial cells, lung function
Abbreviations used : ALI, BAL, BMI, FVC, HDM, LA, LN, MBP, MTEC, OA, OVA, OWA, SP-A, TNF-R, WT
Plan
| Supported by grants HL111151, HL125602, and HL065228. |
|
| Disclosure of potential conflict of interest: N. Lugogo receives grant support from the National Institutes of Health (NIH), Teva, GlaxoSmithKline, Sanofi, AstraZeneca, Genentech, and Grifols and serves as a consultant for Teva. D. Francisco receives grant support from the NIH. A. Manne receives grant support from the NIH. J. L. Ingram receives grant support from the American Lung Association and the American Academy of Allergy, Asthma & Immunology (AAAAI). B. T. Suratt receives royalties from UpToDate. M. E. Sunday is an employee of Duke University. M. Kraft receives grant support from the NIH, Chiesi, and Sanofi; serves as a consultant for Teva Pharmaceutical and AstraZeneca; receives personal fees from FDA Laba Trials and Joint DSMB; and receives royalties from Elsevier. J. G. Ledford receives grant and travel support from the NIH. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 3
P. 918 - mars 2018 Retour au numéro
Article précédent
- Regulatory effects of IL-15 on allergen-induced airway obstruction
- Sathisha Upparahalli Venkateshaiah, Xiang Zhu, Priya Rajavelu, Rituraj Niranjan, Murli Manohar, Alok K. Verma, Joseph A. Lasky, Anil Mishra
- Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps
- Jia Song, Hai Wang, Ya-Na Zhang, Ping-Ping Cao, Bo Liao, Zhe-Zheng Wang, Li-Li Shi, Yin Yao, Guan-Ting Zhai, Zhi-Chao Wang, Li-Meng Liu, Ming Zeng, Xiang Lu, Heng Wang, Xiang-Ping Yang, Di Yu, Claus Bachert, Zheng Liu
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?