Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease

Chana, Kirandeep K.; Fenwick, Peter; Nicholson, Andrew G.; Barnes, Peter J.; Donnelly, Louise E.

doi:10.1016/j.jaci.2013.08.044

Cited by 50 publications

(30 citation statements)

References 50 publications

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“…As reported previously, a majority of the resident cells in the human BAL fluids were CD163-positive AMs (H1; left column of Figure 3A) (18,19). In the allergenchallenged experimental site, the newly recruited eosinophils appeared that were CD163 negative (the second column of Figure 3A); these cells were seen to a lesser degree in the adjacent site (the third column of Figure 3A).…”

Section: Characteristics Of a New Population Of Alveolar Macrophages supporting

confidence: 70%

“…These new macrophages were strongly positive for CD11b and accounted for nearly 80% of the entire CD163-positive AMs. Furthermore, these cells exhibited much stronger expression of CD14 (second in the lower row of Figure 3B; Figure E6), consistent with the recruitment of blood monocytes, which are strongly CD14 positive (19). This recruitment was limited to the allergenchallenged site, with minimal spillover to the immediate adjacent bronchopulmonary subsegment ( Figures 3A and 3B).…”

Section: Characteristics Of a New Population Of Alveolar Macrophages supporting

confidence: 65%

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Recruited Alveolar Macrophages, in Response to Airway Epithelial–Derived Monocyte Chemoattractant Protein 1/CCL2, Regulate Airway Inflammation and Remodeling in Allergic Asthma

Lee

Jeong²,

Nyenhuis

et al. 2015

Am J Respir Cell Mol Biol

151

142

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Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophagedepleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/ MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells.

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Section: Characteristics Of a New Population Of Alveolar Macrophages supporting

confidence: 70%

Section: Characteristics Of a New Population Of Alveolar Macrophages supporting

confidence: 65%

Recruited Alveolar Macrophages, in Response to Airway Epithelial–Derived Monocyte Chemoattractant Protein 1/CCL2, Regulate Airway Inflammation and Remodeling in Allergic Asthma

Lee

Jeong²,

Nyenhuis

et al. 2015

Am J Respir Cell Mol Biol

151

142

View full text Add to dashboard Cite

show abstract

“…However, treatment with corticosteroids have limited effects in reducing inflammatory cell numbers, cytokines, chemokines, or proteases in induced sputum or airway biopsies of patients with COPD and fail to reduce COPD progression, even at high doses [6]. Corticosteroids are also ineffective at suppressing inflammatory proteins in alveolar macrophages from patients with COPD [7].…”

Section: Introductionmentioning

confidence: 99%

A mucoactive drug carbocisteine ameliorates steroid resistance in rat COPD model

Song

Lü

et al. 2016

Pulmonary Pharmacology & Therapeutics

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“…MMPs especially MMP-9 released from alveolar macrophages have been implicated in elastin destruction and development of emphysema (Russell et al 2002b ). Macrophages isolated from patients with COPD contain higher amounts of MMP-9 and are resistant to suppression by glucocorticoids (Chana et al 2014 ). Alveolar macrophages also synthetize and secrete proteinase inhibitors (tissue inhibitors of MP, TIMP).…”

Section: Proteinases and Extracellular Matrix (Ecm) Interactionsmentioning

confidence: 99%

Air Pollution and Chronic Obstructive Airway Disease

Rédai¹,

Haczku

2015

Molecular and Integrative Toxicology

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Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease

Cited by 50 publications

References 50 publications

Recruited Alveolar Macrophages, in Response to Airway Epithelial–Derived Monocyte Chemoattractant Protein 1/CCL2, Regulate Airway Inflammation and Remodeling in Allergic Asthma

Recruited Alveolar Macrophages, in Response to Airway Epithelial–Derived Monocyte Chemoattractant Protein 1/CCL2, Regulate Airway Inflammation and Remodeling in Allergic Asthma

A mucoactive drug carbocisteine ameliorates steroid resistance in rat COPD model

Air Pollution and Chronic Obstructive Airway Disease

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