Obesity impairs apoptotic cell clearance in asthma
Obesity impairs apoptotic cell clearance in asthma
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DOI：
10.1016/j.jaci.2012.09.028
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发表时间：
2013-04-01
影响因子：
14.2
通讯作者：
Sutherland, E. Rand
中科院分区：
文献类型：
--
作者：
Fernandez-Boyanapalli, Ruby;Goleva, Elena;Sutherland, E. Rand
背景资料：与非肥胖成人哮喘相比，肥胖成人哮喘通常更严重，对糖皮质激素的反应更低。在肥胖哮喘患者中，气道巨噬细胞（巨噬细胞增多症）与炎症改变和糖皮质激素敏感性降低有关。我们研究了呼吸道嗜酸性粒细胞增多症（诱导痰）巨噬细胞和血液单核细胞对单核细胞编程的标志物，体外糖皮质激素应答，结果：在肥胖（n = 14）和非肥胖（n = 19）哮喘患者中评估了气道巨噬细胞的胞吐作用。肥胖者的巨噬细胞的胞饮作用比非肥胖者低40%，平均巨噬细胞指数分别为1.77（SD，1.07）和3.00（SD，1.25; P <0.01）。在肥胖参与者的血液单核细胞中观察到类似的单核细胞功能降低。在这些单核细胞中，与红细胞增多症相关的替代（M2）编程标记物的表达也相对减少，包括过氧化物酶体增殖物激活受体δ和CX 3趋化因子受体1。巨噬细胞吞噬指数与地塞米松诱导的丝裂原活化蛋白激酶磷酸酶1表达（p = 0.46，P <0.02）和PBMCs中基线糖皮质激素受体a表达（p = 0.44，P <0.02）显著相关。肥胖哮喘患者血浆4-羟基壬烯醛水平升高至0.33 ng/mL（SD，0.15 ng/mL）vs 0.16 ng/mL非肥胖患者（SD，0.08 ng/mL）（P =.006），并与巨噬细胞吞噬指数呈负相关结论：肥胖成人哮喘与巨噬细胞/单核细胞吞噬功能受损有关。这一过程的损害与单核细胞/巨噬细胞编程改变、糖皮质激素反应性降低和全身氧化应激有关。（J Allergy Clin Immunol 2013; 131：1041 - 7.）
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.)