RETRACTED: Alveolar Macrophages from Overweight/Obese Subjects with Asthma Demonstrate a Proinflammatory Phenotype (Retracted article. See vol. 192, pg. 264, 2015)

被引：56

作者：

Lugogo, Njira L. ^{[1
]}

Hollingsworth, John W. ^{[1
,2
]}

Howell, Druhan L. ^{[3
,4
]}

Que, Loretta G. ^{[1
]}

Francisco, Dave ^{[1
]}

Church, Tony D. ^{[1
]}

Potts-Kant, Erin N. ^{[1
]}

Ingram, Jennifer L. ^{[1
]}

Wang, Ying ^{[1
]}

Jung, Sin-Ho ^{[5
]}

Kraft, Monica ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA

[3] Univ S Alabama, Coll Med, Dept Med, Mobile, AL USA

[4] Univ S Alabama, Coll Med, Dept Pediat, Mobile, AL USA

[5] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2012年 / 186卷 / 05期

关键词：

tumor necrosis factor-alpha; leptin; innate immunity; lipopolysaccharide; environmental lung disease; BODY-MASS INDEX; ADIPOSE-TISSUE; LEPTIN RESISTANCE; INSULIN-RESISTANCE; ADULT ASTHMA; OBESITY; INFLAMMATION; MICE; ASSOCIATION; MECHANISMS;

D O I：

10.1164/rccm.201109-1671OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale Obesity is associated with increased prevalence and severity of asthma. Adipose tissue macrophages can contribute to the systemic proinflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese patients with asthma. Objectives: We hypothesized that leptin levels would be increased in the bronchoalveolar lavage fluid from overweight/obese subjects and, furthermore, that leptin would alter the response of alveolar macrophages to bacterial LPS. Methods: Forty-two subjects with asthma and 46 healthy control subjects underwent research bronchoscopy. Bronchoalveolar lavage fluid from 66 was analyzed for the level of cellular inflammation, cytokines, and soluble leptin. Cultured primary macrophages from 22 subjects were exposed to LPS, leptin, or leptin plus LPS. Cytokines were measured in the supernatants. Measurements and Main Results: Leptin levels were increased in overweight/obese subjects, regardless of asthma status (P = 0.013), but were significantly higher in overweight/obese subjects with asthma. Observed levels of tumor necrosis factor-alpha were highest in overweight/obese subjects with asthma. Ex vivo studies of primary alveolar macrophages indicated that the response to LPS was most robust in alveolar macrophages from overweight/obese subjects with asthma and that preexposure to high-dose leptin enhanced the proinflammatory response. Leptin alone was sufficient to induce production of proinflammatory cytokines from macrophages derived from overweight/obese subjects with asthma. Conclusions: Ex vivo studies indicate that alveolar macrophages derived from overweight/obese subjects with asthma are uniquely sensitive to leptin. This macrophage phenotype, in the context of higher levels of soluble leptin, may contribute to the pathogenesis of airway disease associated with obesity.

引用

页码：404 / 411

页数：8

共 36 条

[1] Obesity and Poor Asthma Control in Patients with Severe Asthma [J].