Phagocytic Dysfunction of Human Alveolar Macrophages and Severity of Chronic Obstructive Pulmonary Disease

Berenson, Charles S.; Kruzel, Ragina L.; Eberhardt, Ellana; Sethi, Sanjay

doi:10.1093/infdis/jit400

Cited by 115 publications

(102 citation statements)

References 38 publications

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“…14, 43 The fact that we observed remarkably reduced E. coli phagocytosis, 5 days after extracellular MWCNT-20 μm were removed, indicates potential for development of similar pathological complications in individuals exposed to such materials.…”

Section: Discussionmentioning

confidence: 65%

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: 65%

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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“…2010; Berenson et al. 2013) as well as THP‐1‐differentiated macrophages and healthy control alveolar macrophages treated with CSE have decreased ability to phagocytose this bacteria (Bozinovski et al. 2011; Hodge et al.…”

Section: Discussionmentioning

confidence: 99%

Phagocytosis and Inflammation: Exploring the effects of the components of E-cigarette vapor on macrophages

et al. 2017

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E‐cigarettes are perceived as harmless; however, evidence of their safety is lacking. New data suggests E‐cigarettes discharge a range of compounds capable of physiological damage to users. We previously established that cigarette smoke caused defective alveolar macrophage phagocytosis. The present study compared the effect E‐cigarette of components; E‐liquid flavors, nicotine, vegetable glycerine, and propylene glycol on phagocytosis, proinflammatory cytokine secretion, and phagocytic recognition molecule expression using differentiated THP‐1 macrophages. Similar to CSE, phagocytosis of NTHi bacteria was significantly decreased by E‐liquid flavoring (11.65–15.75%) versus control (27.01%). Nicotine also decreased phagocytosis (15.26%). E‐liquid, nicotine, and E‐liquid+ nicotine reduced phagocytic recognition molecules; SR‐A1 and TLR‐2. IL‐8 secretion increased with flavor and nicotine, while TNF α, IL‐1β, IL‐6, MIP‐1α, MIP‐1β, and MCP‐1 decreased after exposure to most flavors and nicotine. PG, VG, or PG:VG mix also induced a decrease in MIP‐1α and MIP‐1β. We conclude that E‐cigarettes can cause macrophage phagocytic dysfunction, expression of phagocytic recognition receptors and cytokine secretion pathways. As such, E‐cigarettes should be treated with caution by users, especially those who are nonsmokers.

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“…Preexisting lung disease (e.g., heavy smoking, chronic obstructive pulmonary disease) is the most prevalent underlying condition among patients with pulmonary M. kansasii infections (34). Underlying lung conditions likely increase susceptibility to infection due to impaired alveolar macrophage phagocytic activity (35) and immune responses (36). However, the lack of association between underlying lung disease alone and disseminated M. kansasii disease (34) suggests that extrapulmonary immune responses largely remain intact in these patients.…”

Section: Discussionmentioning

confidence: 99%

Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency

et al. 2016

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Rationale: Mycobacterium kansasii usually causes chronic pulmonary infections in immunocompetent patients. In contrast, disseminated M. kansasii disease is commonly associated with advanced human immunodeficiency virus infection, but is reported infrequently in other immunocompromised patients.Objectives: To identify common clinical manifestations and potential risk factors for M. kansasii infection in patients with GATA2 deficiency.Methods: We reviewed M. kansasii disease associated with GATA2 deficiency at one institution and disease associated with primary and other immunodeficiencies reported in the literature. Measurements and Main Results:Nine patients with GATA2 deficiency developed M. kansasii infections. Six patients developed disseminated disease. All patients presented with significant mediastinal lymphadenopathy or abscesses. Seven patients had pulmonary risk factors, including six smokers. The majority of patients had low numbers of neutrophils, monocytes, B cells, CD4 1 T cells, and natural killer cells. Other conditions associated with disseminated M. kansasii disease were thymic disorders and IFN-g/IL-12 defects.Conclusions: Disseminated M. kansasii disease involving mediastinal lymph nodes is surprisingly common in GATA2 deficiency, but also occurs in defects of IFN-g synthesis and response. Disseminated M. kansasii should be considered a marker indicating a need to evaluate for immunodeficiency syndromes.

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Phagocytic Dysfunction of Human Alveolar Macrophages and Severity of Chronic Obstructive Pulmonary Disease

Cited by 115 publications

References 38 publications

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

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

Phagocytosis and Inflammation: Exploring the effects of the components of E-cigarette vapor on macrophages

Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency

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