Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype

Njira L. Lugogo, John W. Hollingsworth, Druhan L. Howell, Loretta G. Que, Dave Francisco, Tony D. Church, Erin N. Potts-Kant, Jennifer L. Ingram, Ying Wang, Sin Ho Jung, Monica Kraft

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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-a 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.

Original languageEnglish (US)
Pages (from-to)404-411
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume186
Issue number5
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Fingerprint

Bronchoalveolar Lavage Fluid
Alveolar Macrophages
Bronchoscopy
Leptin
Innate Immunity
Lipopolysaccharides
Case-Control Studies
Young Adult
Cultured Cells
Linear Models
Analysis of Variance
Asthma
Tumor Necrosis Factor-alpha
Obesity
Biomarkers
Enzyme-Linked Immunosorbent Assay
Cytokines
Phenotype
Macrophages
Adipose Tissue

Keywords

  • Environmental lung disease
  • Innate immunity
  • Leptin
  • Lipopolysaccharide
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype. / Lugogo, Njira L.; Hollingsworth, John W.; Howell, Druhan L.; Que, Loretta G.; Francisco, Dave; Church, Tony D.; Potts-Kant, Erin N.; Ingram, Jennifer L.; Wang, Ying; Jung, Sin Ho; Kraft, Monica.

In: American journal of respiratory and critical care medicine, Vol. 186, No. 5, 01.09.2012, p. 404-411.

Research output: Contribution to journalArticle

Lugogo, NL, Hollingsworth, JW, Howell, DL, Que, LG, Francisco, D, Church, TD, Potts-Kant, EN, Ingram, JL, Wang, Y, Jung, SH & Kraft, M 2012, 'Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype', American journal of respiratory and critical care medicine, vol. 186, no. 5, pp. 404-411. https://doi.org/10.1164/rccm.201109-1671OC
Lugogo, Njira L. ; Hollingsworth, John W. ; Howell, Druhan L. ; Que, Loretta G. ; Francisco, Dave ; Church, Tony D. ; Potts-Kant, Erin N. ; Ingram, Jennifer L. ; Wang, Ying ; Jung, Sin Ho ; Kraft, Monica. / Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype. In: American journal of respiratory and critical care medicine. 2012 ; Vol. 186, No. 5. pp. 404-411.
@article{01406a5111dd49f09d4230077732e22e,
title = "Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype",
abstract = "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-a 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.",
keywords = "Environmental lung disease, Innate immunity, Leptin, Lipopolysaccharide, Tumor necrosis factor-α",
author = "Lugogo, {Njira L.} and Hollingsworth, {John W.} and Howell, {Druhan L.} and Que, {Loretta G.} and Dave Francisco and Church, {Tony D.} and Potts-Kant, {Erin N.} and Ingram, {Jennifer L.} and Ying Wang and Jung, {Sin Ho} and Monica Kraft",
year = "2012",
month = "9",
day = "1",
doi = "10.1164/rccm.201109-1671OC",
language = "English (US)",
volume = "186",
pages = "404--411",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "5",

}

TY - JOUR

T1 - Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype

AU - Lugogo, Njira L.

AU - Hollingsworth, John W.

AU - Howell, Druhan L.

AU - Que, Loretta G.

AU - Francisco, Dave

AU - Church, Tony D.

AU - Potts-Kant, Erin N.

AU - Ingram, Jennifer L.

AU - Wang, Ying

AU - Jung, Sin Ho

AU - Kraft, Monica

PY - 2012/9/1

Y1 - 2012/9/1

N2 - 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-a 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.

AB - 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-a 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.

KW - Environmental lung disease

KW - Innate immunity

KW - Leptin

KW - Lipopolysaccharide

KW - Tumor necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=84865824614&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865824614&partnerID=8YFLogxK

U2 - 10.1164/rccm.201109-1671OC

DO - 10.1164/rccm.201109-1671OC

M3 - Article

C2 - 22773729

AN - SCOPUS:84865824614

VL - 186

SP - 404

EP - 411

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 5

ER -