Macrophages and the Pathogenesis of COPD

Tetley, Teresa D.

doi:10.1378/chest.121.5_suppl.156s

Cited by 168 publications

(123 citation statements)

References 17 publications

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“…IL-8 release by AMs was also significantly increased 1 day after treatment with MWCNT-20 μm; interestingly however, this increase had resolved at 5 days posttreatment time point. IL-6 is a pleiotropic cytokine associated with the pathogenesis of numerous lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis, 31,32 while IL-8 is a potent chemoattractant for neutrophils and is generally associated with acute inflammation 33 but which is also elevated in chronic inflammatory lung diseases, such as COPD, where the elevated circulating levels of IL-6 and IL-8 are proposed to be predominantly AM derived, 34,35 therefore there are important pathological consequences for increases in these mediators from MWCNT-treated AMs. For those AMs that remained viable 1 and 5 days after the 24-hour treatment with MWCNT-0.6 μm or MWCNT-20 μm, we were interested in determining their functional capabilities in terms of bacterial phagocytosis (important for maintaining alveolar sterility) and migration (important for removal of phagocytosed material from the alveolar unit).…”

Section: Discussionmentioning

confidence: 99%

Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes

Sweeney¹,

Grandolfo²,

Ruenraroengsak³

et al. 2015

IJN

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Purpose: Multiwalled carbon nanotubes (MWCNTs) are a potential human health hazard, primarily via inhalation. In the lung, alveolar macrophages (AMs) provide the first line of immune cellular defense against inhaled materials. We hypothesized that, 1 and 5 days after treating AMs with short (0.6 μm in length; MWCNT-0.6 μm) and long (20 μm in length; MWCNT-20 μm) MWCNTs for 24 hours, AMs would exhibit increased markers of adverse bioreactivity (cytokine release and reactive oxygen species generation) while also having a modified functional ability (phagocytosis and migration). Methods: Primary human AMs were treated with short and long MWCNTs for 24 hours, 1 and 5 days after which toxicity end points, including cell death, reactive oxygen species generation, and inflammatory mediator release, were measured. AM functional end points involving phagocytic ability and migratory capacity were also measured. Results: AM viability was significantly decreased at 1 and 5 days after treatment with MWCNT-20 μm, while superoxide levels and inflammatory mediator release were significantly increased. At the same time, there was reduced phagocytosis and migratory capacity alongside increased expression of MARCO; this coincided with frustrated phagocytosis observed by scanning electron microscopy. In contrast, the adverse bioreactivity of the shorter MWCNT-0.6 μm with AMs (and any resulting reduction in AM functional ability) was substantially less marked or absent altogether. Conclusion:This study shows that after 24-hour treatment with long, but not short, MWCNTs, AM function is severely affected up to 5 days after the initial exposure. This has potentially significant pathophysiological consequences for individuals who may be intentionally (via therapeutic applications) or unintentionally exposed to these nanomaterials.

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Section: Discussionmentioning

confidence: 99%

Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes

Sweeney¹,

Grandolfo²,

Ruenraroengsak³

et al. 2015

IJN

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“…Alveolar macrophages have long been considered as central orchestrators of the inflammatory response in COPD due to the observed increase in macrophage numbers present in the lungs of patients and a strong correlation between levels of infiltration and disease progression (6,7). In addition, the infiltrating macrophages are found to be localised to areas of tissue damage and can express a wide array of proinflammatory mediators (17).…”

Section: Alveolar Macrophagesmentioning

confidence: 99%

“…The relatively large numbers of macrophages and neutrophils present in the airways of COPD patients has contributed to the hypothesis that both cell types are critical mediators of disease pathogenesis (5)(6)(7). Neutrophils, through the release of elastases and reactive oxygen species are thought to play a significant role in tissue destruction while macrophages have also been implicated in promoting alveolar airspace enlargement, primarily through the release of matrix metalloproteinases (MMPs).…”

Section: Introductionmentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease: Evidence for an Autoimmune Component

Stefańska

Walsh

2009

Cell Mol Immunol

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Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible limitation on pulmonary airflow associated with chronic inflammation and mucous hypersecretion (chronic bronchitis) and/or the pathological destruction of alveolar airspaces leading to emphysema. COPD, predominantly as a result of tobacco smoke exposure, represents the fourth leading cause of mortality worldwide and its prevalence is increasing. Despite this, much of the basic mechanisms which contribute to disease progression remain to be elucidated and current therapeutic approaches are, for the most part, based upon alleviating patient symptoms (bronchodilators) as opposed to treating the underlying pathological mechanisms triggered in response to cigarette smoke exposure. The classic disease paradigm suggests that an imbalance of pulmonary matrix proteases versus anti-proteases underlies the tissue destruction and inflammation associated with COPD. However, there is a growing appreciation of the complex and multifaceted nature of the pathological mechanisms associated with disease progression. Recently, there has been mounting evidence indicating that COPD patients exhibit many of the characteristics of a classical autoimmune response. We will discuss current evidence in support of this paradigm and outline how future therapeutic approaches may be tailored to address this. Cellular & Molecular Immunology. 2009;6(2):81-86.

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“…Smoking is recognised as a critical initiating insult to the bronchial epithelium, triggering a strong pulmonary innate immune response, in those who develop COPD and lung cancer [14][15][16]. However, there is also evidence that systemic inflammation plays a primary role in the development (and possibly progression) of these diseases [15,16].…”

Section: Systemic Inflammation In the Copd-lung Cancer Linkmentioning

confidence: 99%