Obesity impairs apoptotic cell clearance in asthma - 30/03/13
, E. Rand Sutherland, MD, MPH b, d, ⁎ 
Corresponding author: E. Rand Sutherland, MD, MPH, 1400 Jackson St, J-201, Denver, CO 80206.Abstract |
Background |
Asthma in obese adults is typically more severe and less responsive to glucocorticoids than asthma in nonobese adults.
Objective |
We sought to determine whether the clearance of apoptotic inflammatory cells (efferocytosis) by airway macrophages was associated with altered inflammation and reduced glucocorticoid sensitivity in obese asthmatic patients.
Methods |
We investigated the relationship of efferocytosis by airway (induced sputum) macrophages and blood monocytes to markers of monocyte programming, in vitro glucocorticoid response, and systemic oxidative stress in a cohort of adults with persistent asthma.
Results |
Efferocytosis by airway macrophages was assessed in obese (n = 14) and nonobese (n = 19) asthmatic patients. Efferocytosis by macrophages was 40% lower in obese than nonobese subjects, with a mean efferocytic index of 1.77 (SD, 1.07) versus 3.00 (SD, 1.25; P < .01). A similar reduction of efferocytic function was observed in blood monocytes of obese participants. In these monocytes there was also a relative decrease in expression of markers of alternative (M2) programming associated with efferocytosis, including peroxisome proliferator-activated receptor δ and CX3 chemokine receptor 1. Macrophage efferocytic index was significantly correlated with dexamethasone-induced mitogen-activated protein kinase phosphatase 1 expression (ρ = 0.46, P < .02) and baseline glucocorticoid receptor ⍺ expression (ρ = 0.44, P < .02) in PBMCs. Plasma 4-hydroxynonenal levels were increased in obese asthmatic patients at 0.33 ng/mL (SD, 0.15 ng/mL) versus 0.16 ng/mL (SD, 0.08 ng/mL) in nonobese patients (P = .006) and was inversely correlated with macrophage efferocytic index (ρ = −0.67, P = .02).
Conclusions |
Asthma in obese adults is associated with impaired macrophage/monocyte efferocytosis. Impairment of this anti-inflammatory process is associated with altered monocyte/macrophage programming, reduced glucocorticoid responsiveness, and systemic oxidative stress.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, obesity, inflammation, macrophage, oxidative stress, steroid
Abbreviations used : ADAM, BMI, GCR, 4HNE, MKP-1, PPAR
Plan
| Supported by HL090982, the National Jewish Health Translational Pilot Program, HL34303, AI058228, UL1 RR025780, Catherine Kramer Scientist in Pediatric Medicine, the Max Goldenberg Foundation, the Walter S. and Lucienne B. Driskill Charitable Foundation, and the Eugene F. and Easton M. Crawford Charitable Lead Unitrust. |
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| Disclosure of potential conflict of interest: R. Fernandez-Boyanapalli has been supported by one or more grants from the Crawford Charitable Lead Unitrust. E. Goleva has been supported by one or more grants from the National Institutes of Health (NIH). B. Day has consultancy arrangements with Aeolus Pharmaceuticals; has received one or more grants from or has one or more grants pending with the NIH (RO1 ES017582 and U54 ES015678) and the Cystic Fibrosis Foundation; has one or more patents (planned, pending, or issued) with Saber Pharmaceuticals (US#6,231,894) and Aeolus Pharmaceuticals (US#5,994,339; #6,127,356; #6,479,477; #6,583,132; #6,916,799; #7,189,707; #7,470,677; #7,820,644; #8,217,026); and owns stock/stock options in Aeolus Pharmaceuticals. D. L. Bratton has been supported by one or more grants from the Catherine Kramer Foundation (endowed chair in pediatric medicine); has been supported by one or more grants from National Jewish Health (Translational Pilot Grant Program support for the investigation); is employed by National Jewish Health; and has received one or more payments for lecturing from or is on the speakers’ bureau for the American Thoracic Society and the American Academy of Allergy, Asthma & Immunology. E. R. Sutherland has consultancy arrangements with Forest Laboratories, GlaxoSmithKline, Merck/Schering-Plough, Novartis (inactive), Dey (inactive), and Genentech; is employed by National Jewish Health; has received one or more grants from or has one or more grants pending with Boehringer-Ingelheim, Novartis, and the National Institutes of Health; and has received one or more payments for the development of educational presentations for Genentech. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 4
P. 1041 - avril 2013 Retour au numéro
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