Mechanisms of allergy and clinical immunologyIdentification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease
Section snippets
Subject selection
Lung tissue surplus to diagnostic requirements was obtained from pulmonary resections at the Royal Brompton and Harefield NHS Foundation Trust. Smokers had a smoking history of at least 10 pack years, and patients with COPD were stable and fulfilled the American Thoracic Society criteria.27 All subjects provided written informed consent, as approved by the London-Chelsea Research Ethics Committee. There were significant differences between FEV1 in liters, FEV1 percent predicted, and FEV1/forced
Results
Approximately 90% of cells extracted from the 10% to 20% (vol/vol) and 20% to 30% (vol/vol) Percoll interfaces were nonviable, resulting in their exclusion from further analysis (Table II). Cell viability increased with increasing cell density, with greater than 70% of cells viable in the remaining cell fractions (Table II). Cells from the 3 remaining viable fractions had clearly defined nuclei and cytoplasm reminiscent of macrophages with no clear morphological differences (see Fig E2 in this
Discussion
Macrophages play a pivotal role in the pathophysiology of COPD, in which alveolar macrophages increase in number, release more inflammatory mediators (eg, CXCL8, TNF-α, and MMP-9), and respond less well to glucocorticosteroids.6, 32 This study investigated the possibility that these macrophages might represent a distinct phenotype associated with COPD and showed that within the pulmonary macrophage population, approximately a third of these cells are glucocorticosteroid insensitive and release
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2020, Respiratory InvestigationCitation Excerpt :M1 macrophages accumulate and evoke inflammation, which leads to epithelial-mesenchymal transition (EMT), tumor angiogenesis, and basal membrane disruption via inflammatory cytokines such as TNF-α, TGF-β, or IL-6 [14,15]. M1 macrophages also accumulate in the airway and alveoli of COPD patients, which induces chronic inflammation via similar cytokines [16,17]. Second, cigarette smoking and the subsequent oxidative stress are common extrinsic risk factors in urothelial cancer and COPD.
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2019, CytokineCitation Excerpt :M1 macrophages have pro-inflammatory and cytotoxic properties, and M2 macrophages have anti-inflammatory and tissue repair functions [24]. This model however is simplistic, as macrophages may have both M1 and M2 characteristics, and Chana et al reported that COPD macrophages can have both M1 and M2 properties [25]. Furthermore, distinct subpopulations of macrophages exist in the lower airways of COPD patients and controls [19]; Small interstitial macrophages that are pro-inflammatory, small alveolar macrophages that are highly phagocytic and large alveolar macrophages with low pro-inflammatory and phagocytic ability have been identified [19].
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Supported by a studentship from the BBSRC, United Kingdom. Also supported by the National Institute of Health Research Respiratory Disease Biomedical Research Unit at the Royal Brompton Hospital and Harefield Foundation NHS Trust and Imperial College London.
Disclosure of potential conflict of interest: P. J. Barnes has been supported by one or more grants from GlaxoSmithKline and AstraZeneca; is a Board member for Boehringer Ingelheim and Pfizer, has consultancy arrangements with Glenmark and Sun Pharma; has provided expert testimony for Boehringer Ingelheim and TEVA; has received one or more grants from or has one or more grants pending with AstraZeneca, Nycomed/Takeda, Novartis, Boehringer Ingelheim, Chiesi, Aquinox, and Pfizer; and has received one or more payments for lecturing from or is on the speakers' bureau for AstraZeneca, Nycomed, Chiesi, Novartis, and Pfizer. L. E. Donnelly has been supported by one or more grants from BBSRC, Pfizer, MRC, Boehringer Ingelheim, Nycomed, and AstraZeneca. The rest of the authors declare that they have no relevant conflicts of interest.