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J Allergy Clin Immunol. 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.

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  • 1Department of Pediatrics, National Jewish Health, University of Colorado School of Medicine, Denver, CO 80206, USA.

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.

PMID:
23154082
PMCID:
PMC4190068
DOI:
10.1016/j.jaci.2012.09.028
[PubMed - indexed for MEDLINE]
Free PMC Article

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