Dataset Information

Phenotypic characterization of lung macrophages in asthmatic patients: overexpression of CCL17.

ABSTRACT:

Background

Studies with monocyte-derived macrophages (MDMs) and animal models have suggested a role for alternatively activated (M2) macrophages in asthmatic inflammation, but in vivo evidence for this phenotype in human asthma is lacking.

Objective

To characterize the phenotype of lung macrophages from asthmatic patients in relation to disease severity and treatment.

Methods

M2 biomarkers were first identified by using MDMs exposed to T(H)2 cytokines and then used to phenotype sputum and bronchoalveolar lavage (BAL) macrophages from 12 healthy control subjects, 12 patients with mild asthma, and 14 patients with moderate asthma and to assess the effects of corticosteroids and phosphatidylinositol 3-kinase (PI3K) inhibitors.

Results

Sputum macrophages from asthmatic patients expressed significantly more CCL17 mRNA but less CD163 than macrophages from healthy subjects. However, none of the other M2 biomarkers were differentially expressed in asthmatic patients, and ex vivo BAL cells spontaneously produced similar amounts of M2 cytokines/chemokines (IL-10, CCL17, and CCL22). CCL17 mRNA overexpression correlated weakly but significantly with sputum eosinophilia (P = .0252) and was also observed in macrophages from patients with moderate asthma treated with inhaled steroids, suggesting relative insensitivity to inhibition by corticosteroids. The PI3K inhibitor LY294002 inhibited basal CCL17 release from BAL cells and IL-4-stimulated release from MDMs.

Conclusions

This study does not support the existence in human asthma of the full M2 phenotype described to date but points to upregulation of CCL17 in both patients with mild and those with moderate asthma, providing a further source for this ligand of CCR4(+) cells that contributes to airways inflammation. CCL17 expression is corticosteroid resistant but suppressed by PI3K enzyme inhibitors.

SUBMITTER: Staples KJ

PROVIDER: S-EPMC3805016 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

Phenotypic characterization of lung macrophages in asthmatic patients: overexpression of CCL17.

Staples Karl J KJ Hinks Timothy S C TS Ward Jon A JA Gunn Victoria V Smith Caroline C Djukanović Ratko R

The Journal of allergy and clinical immunology 20120914 6

<h4>Background</h4>Studies with monocyte-derived macrophages (MDMs) and animal models have suggested a role for alternatively activated (M2) macrophages in asthmatic inflammation, but in vivo evidence for this phenotype in human asthma is lacking.<h4>Objective</h4>To characterize the phenotype of lung macrophages from asthmatic patients in relation to disease severity and treatment.<h4>Methods</h4>M2 biomarkers were first identified by using MDMs exposed to T(H)2 cytokines and then used to pheno ...[more]

PMID: 22981793

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Project description:PURPOSE:It is difficult to assess airway obstruction using spirometry in adult asthmatic patients with preserved lung function. Impulse oscillometry (IOS) can detect not only airway resistance but also reactance. Therefore, IOS may be useful in assessing pulmonary function in such patients. We investigated the applicability of IOS for asthma patients with preserved lung function. METHODS:Between 2015 and 2018, 1,248 adult asthmatic patients suspected of having asthma who visited the Allergy and Asthma Center of Severance Hospital underwent both spirometry and IOS. Consequently, 784 patients had asthma, 111 had chronic obstructive lung disease (COPD) or asthma-COPD overlap, and 7 had parenchymal lung disease. The remaining 346 patients had chronic cough without underlying lung or airway disease. Among the 784 asthmatic patients, 191 with decreased lung function (predicted forced expiratory volume in 1 second [FEV1] < 80%) were excluded. Propensity score matching was performed to adjust baseline characteristics between 346 non-asthmatic and 593 asthmatic patients with preserved lung function. Subsequently, we compared the spirometry and IOS parameters between the 329 asthmatic and 329 non-asthmatic patients. RESULTS:Multiple logistic regression analysis showed that the area of reactance (AX) was associated with asthma with preserved lung function. In receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) of AX (AUC = 0.6823) for asthma was not significantly different from that of FEV1 (AUC = 0.6758). However, the AUC of a combination of AX and FEV1 (AUC = 0.7437) for asthma was significantly higher than that of FEV1 alone. The cutoff value of AX was 0.51 kPa/L in univariate ROC analysis. CONCLUSIONS:AX is associated with adult asthma with preserved lung function. Performing spirometry together with IOS is more beneficial than performing spirometry alone for diagnosing asthma in adult patients with preserved lung function.

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Dataset Information

Phenotypic characterization of lung macrophages in asthmatic patients: overexpression of CCL17.

Background

Objective

Methods

Results

Conclusions

Publications

Phenotypic characterization of lung macrophages in asthmatic patients: overexpression of CCL17.

Similar Datasets

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