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. 2013 Apr;131(4):1041-7, 1047.e1-3.
doi: 10.1016/j.jaci.2012.09.028. Epub 2012 Nov 13.

Obesity impairs apoptotic cell clearance in asthma

Ruby Fernandez-Boyanapalli  1 , Elena Goleva, Christena Kolakowski, Elysia Min, Brian Day, Donald Y M Leung, David W H Riches, Donna L Bratton, E Rand Sutherland
Affiliations

Obesity impairs apoptotic cell clearance in asthma

Ruby Fernandez-Boyanapalli et al. J Allergy Clin Immunol. 2013 Apr.

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 α 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.

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Conflict of interest statement

Disclosure of potential conflict of interest: The rest of the authors declare that they have no relevant conflicts of interest.

Figures

FIG 1
FIG 1
4HNE concentrations in the plasma of nonobese (n = 10) and obese (n = 10) asthmatic patients.
See this image and copyright information in PMC

References

    1. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752–1761. - PMC - PubMed
    1. Keaney JF, Larson MG, Vasan RS, Wilson PWF, Lipinska I, Corey D, et al. Obesity and systemic oxidative stress. Arterioscler Thromb Vasc Biol. 2003;23:434–439. - PubMed
    1. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219–246. - PubMed
    1. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85–97. - PMC - PubMed
    1. Webster JC, Oakley RH, Jewell CM, Cidlowski JA. Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative beta isoform: a mechanism for the generation of glucocorticoid resistance. Proc Natl Acad Sci U S A. 2001;98:6865–6870. - PMC - PubMed

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