Obesity impairs apoptotic cell clearance in asthma

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:131

Article

Fernandez-Boyanapalli, Ruby¹  Goleva, Elena¹  Kolakowski, Christena²  Min, Elysia²  Day, Brian²  Leung, Donald Y. M.^1,3  Riches, David W. H.^1,4,5  Bratton, Donna L.^1,3  Sutherland, E. Rand^2,4 

[1] Natl Jewish Hlth, Sch Med, Dept Pediat, Denver, CO USA

[2] Natl Jewish Hlth, Sch Med, Dept Med, Denver, CO USA

[3] Univ Colorado, Sch Med, Dept Pediat, Denver, CO USA

[4] Univ Colorado, Sch Med, Dept Med, Denver, CO USA

[5] Univ Colorado, Sch Med, Dept Immunol, Denver, CO USA

关键词: Asthma;    obesity;    inflammation;    macrophage;    oxidative stress;    steroid;   

DOI  :  10.1016/j.jaci.2012.09.028

来源: Elsevier

【 摘 要 】

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 delta and CX3 chemokine receptor 1. Macrophage efferocytic index was significantly correlated with dexamethasone-induced mitogen-activated protein kinase phosphatase 1 expression (p = 0.46, P < .02) and baseline glucocorticoid receptor a expression (p = 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 (p = 5 20.67, P = .02). Conclusions: Asthma in obese adults is associated with impaired macrophage/monocyte efferocytosis. Impairment of this antiinflammatory process is associated with altered monocyte/macrophage programming, reduced glucocorticoid responsiveness, and systemic oxidative stress. (J Allergy Clin Immunol 2013; 131:1041-7.)

【 授权许可】

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