Regulation of Macrophage Foam Cell Formation During Nitrogen Mustard (NM)-Induced Pulmonary Fibrosis by Lung Lipids

Venosa, Alessandro; Smith, L. Cody; Murray, Alexa; Banota, Tanvi; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

doi:10.1093/toxsci/kfz187

Cited by 32 publications

(33 citation statements)

References 86 publications

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“…Chronologically, histochemical and biological onset of fibrosis occurred after AM lipid accumulation had started. Fibrosis subsequent to nitrogen mustard exposure triggered the transformation of AM into foam cells [138], and in this case, lipid-laden pulmonary macrophages also showed altered lipid handling pathways as analyzed by RNAseq.…”

Section: Lipids In Interstitial Lung Disease and Idiopathic Pulmonarymentioning

confidence: 86%

Alveolar lipids in pulmonary disease. A review

2020

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Lung lipid metabolism participates both in infant and adult pulmonary disease. The lung is composed by multiple cell types with specialized functions and coordinately acting to meet specific physiologic requirements. The alveoli are the niche of the most active lipid metabolic cell in the lung, the type 2 cell (T2C). T2C synthesize surfactant lipids that are an absolute requirement for respiration, including dipalmitoylphosphatidylcholine. After its synthesis and secretion into the alveoli, surfactant is recycled by the T2C or degraded by the alveolar macrophages (AM). Surfactant biosynthesis and recycling is tightly regulated, and dysregulation of this pathway occurs in many pulmonary disease processes. Alveolar lipids can participate in the development of pulmonary disease from their extracellular location in the lumen of the alveoli, and from their intracellular location in T2C or AM. External insults like smoke and pollution can disturb surfactant homeostasis and result in either surfactant insufficiency or accumulation. But disruption of surfactant homeostasis is also observed in many chronic adult diseases, including chronic obstructive pulmonary disease (COPD), and others. Sustained damage to the T2C is one of the postulated causes of idiopathic pulmonary fibrosis (IPF), and surfactant homeostasis is disrupted during fibrotic conditions. Similarly, surfactant homeostasis is impacted during acute respiratory distress syndrome (ARDS) and infections. Bioactive lipids like eicosanoids and sphingolipids also participate in chronic lung disease and in respiratory infections. We review the most recent knowledge on alveolar lipids and their essential metabolic and signaling functions during homeostasis and during some of the most commonly observed pulmonary diseases.

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Section: Lipids In Interstitial Lung Disease and Idiopathic Pulmonarymentioning

confidence: 86%

Alveolar lipids in pulmonary disease. A review

2020

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“…The formation of foam cells (lipid-filled macrophages) is generally associated with the pathogenesis of cardiovascular diseases, such as atherosclerosis. However, foam cells are also found in patients with silicosis ( 241 ) and other fibrotic lung diseases ( 242 ) and in tuberculosis. Alveolar macrophages take up extracellular and intracellular lipids in response to inhaled silica, vaping products ( 243 ), and Mycobacterium tuberculosis ( 244 ).…”

Section: Effects Of Androgen Exposure On Monocytes Macrophages mentioning

confidence: 99%

Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung

2020

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Androgens, the predominant male sex hormones, drive the development and maintenance of male characteristics by binding to androgen receptor (AR). As androgens are systemically distributed throughout the whole organism, they affect many tissues and cell types in addition to those in male sexual organs. It is now clear that the immune system is a target of androgen action. In the lungs, many immune cells express ARs and are responsive to androgens. In this review, we describe the effects of androgens and ARs on lung myeloid immune cells-monocytes and macrophages-as they relate to health and disease. In particular, we highlight the effect of androgens on lung diseases, such as asthma, chronic obstructive pulmonary disease and lung fibrosis. We also discuss the therapeutic use of androgens and how circulating androgens correlate with lung disease. In addition to human studies, we also discuss how mouse models have helped to uncover the effect of androgens on monocytes and macrophages in lung disease. Although the role of estrogen and other female hormones has been broadly analyzed in the literature, we focus on the new perspectives of androgens as modulators of the immune system that target myeloid cells during lung inflammation.

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“…Interestingly, in line with our findings regarding LXR/RXR and FXR/RXR and the differentiation and activation of macrophages in IPF [ 20 ], Venosa et al reported that treatment with fibrotic substances induces a time-related increase in large vacuolated macrophages and the accumulation of oxidized phospholipids in lung macrophages and epithelial cells, promoting the formation of foamy macrophages and their M2 activation. This treatment also increases phospholipids and cholesterol in BAL fluid, with evident alteration of lipid-handling pathways under the control of the transcription factors LXR, FXR, PPAR-γ and sterol regulatory element-binding protein [ 89 ].…”

Section: Onset Of Fibrosis: the Contribution Of Dysregulated Lipidmentioning

confidence: 99%

Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis

Bargagli

Refini

d’Alessandro

et al. 2020

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disorder limited to the lung. New findings, starting from our proteomics studies on IPF, suggest that systemic involvement with altered molecular mechanisms and metabolic disorder is an underlying cause of fibrosis. The role of metabolic dysregulation in the pathogenesis of IPF has not been extensively studied, despite a recent surge of interest. In particular, our studies on bronchoalveolar lavage fluid have shown that the renin–angiotensin–aldosterone system (RAAS), the hypoxia/oxidative stress response, and changes in iron and lipid metabolism are involved in onset of IPF. These processes appear to interact in an intricate manner and to be related to different fibrosing pathologies not directly linked to the lung environment. The disordered metabolism of carbohydrates, lipids, proteins and hormones has been documented in lung, liver, and kidney fibrosis. Correcting these metabolic alterations may offer a new strategy for treating fibrosis. This paper focuses on the role of metabolic dysregulation in the pathogenesis of IPF and is a continuation of our previous studies, investigating metabolic dysregulation as a new target for fibrosis therapy.

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Regulation of Macrophage Foam Cell Formation During Nitrogen Mustard (NM)-Induced Pulmonary Fibrosis by Lung Lipids

Cited by 32 publications

References 86 publications

Alveolar lipids in pulmonary disease. A review

Alveolar lipids in pulmonary disease. A review

Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung

Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis

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