Possible Implication of Hypoxia-mediated Incomplete Neutrophil Extracellular Trap Formation in Pneumonia-induced Exacerbation of Lung Diseases

Abstract When patients with preexisting lung diseases, such as chronic obstructive pulmonary disease, interstitial pneumonitis, and pulmonary arterial hypertension, develop pneumonia, the complication often exacerbates the underlying diseases. Although neutrophil extracellular traps (NETs) are important components of innate immune system, the residue of NETs in the tissue can harm the host. We examined the expression of hypoxia-inducible factor 1α (HIF-1α) and NETs in the lungs of patients with lung diseases complicated with pneumonia, and investigated the properties of NETs generated under hypoxia. This study demonstrated that the amount of NETs in pulmonary lesions was greater in patients with pneumonia than in patients without pneumonia and displayed a positive correlation between the amount of NETs and HIF-1α expression. We further demonstrated that the formation of typical lytic NETs was suppressed and round-shaped NETs were generated under hypoxic conditions in vitro. These round NETs were resistant to digestion by the principal NET regulator, DNase I. Focusing on actin rearrangement in neutrophils stimulated under hypoxic conditions, we found that G-actin polymerization and F-actin degradation—both of which are observed time-dependently under normoxic conditions—were disrupted, suggesting that hypoxia mediated the incomplete NET formation. Moreover, neutrophils stimulated under hypoxic conditions possessed cytotoxicity. Accumulation of neutrophils that form degradation-resistant NETs and possess cytotoxicity, which are generated under hypoxic circumstances, are expected to be involved in exacerbation of underlying lung diseases complicated with pneumonia.

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New Insights into the Implication of Mitochondrial Dysfunction in Tissue, Peripheral Blood Mononuclear Cells, and Platelets during Lung Diseases

Journal of Clinical Medicine ◽

10.3390/jcm9051253 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1253 ◽

Cited By ~ 1

Author(s):

Marianne Riou ◽

Abrar Alfatni ◽

Anne-Laure Charles ◽

Emmanuel Andrès ◽

Cristina Pistea ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Arterial Hypertension ◽

Blood Cells ◽

Lung Diseases ◽

Mononuclear Cells ◽

Chronic Obstructive ◽

Peripheral Blood Mononuclear ◽

Obstructive Pulmonary Disease ◽

Blood Mononuclear Cells ◽

Pulmonary Arterial

Lung diseases such as chronic obstructive pulmonary disease, asthma, pulmonary arterial hypertension, or idiopathic pulmonary fibrosis are major causes of morbidity and mortality. Complex, their physiopathology is multifactorial and includes lung mitochondrial dysfunction and enhanced reactive oxygen species (ROS) release, which deserves increased attention. Further, and importantly, circulating blood cells (peripheral blood mononuclear cells-(PBMCs) and platelets) likely participate in these systemic diseases. This review presents the data published so far and shows that circulating blood cells mitochondrial oxidative capacity are likely to be reduced in chronic obstructive pulmonary disease (COPD), but enhanced in asthma and pulmonary arterial hypertension in a context of increased oxidative stress. Besides such PBMCs or platelets bioenergetics modifications, mitochondrial DNA (mtDNA) changes have also been observed in patients. These new insights open exciting challenges to determine their role as biomarkers or potential guide to a new therapeutic approach in lung diseases.

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Extracellular Vesicles from Airway Secretions: New Insights in Lung Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22020583 ◽

2021 ◽

Vol 22 (2) ◽

pp. 583

Author(s):

Laura Pastor ◽

Elisabeth Vera ◽

Jose M. Marin ◽

David Sanz-Rubio

Keyword(s):

Extracellular Vesicles ◽

Lung Diseases ◽

Biomarker Discovery ◽

Cell Communication ◽

Membrane Vesicles ◽

Lavage Fluid ◽

In Vitro Models ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease

Lung diseases (LD) are one of the most common causes of death worldwide. Although it is known that chronic airway inflammation and excessive tissue repair are processes associated with LD such as asthma, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), their specific pathways remain unclear. Extracellular vesicles (EVs) are heterogeneous nanoscale membrane vesicles with an important role in cell-to-cell communication. EVs are present in general biofluids as plasma or urine but also in secretions of the airway as bronchoalveolar lavage fluid (BALF), induced sputum (IS), nasal lavage (NL) or pharyngeal lavage. Alterations of airway EV cargo could be crucial for understanding LD. Airway EVs have shown a role in the pathogenesis of some LD such as eosinophil increase in asthma, the promotion of lung cancer in vitro models in COPD and as biomarkers to distinguishing IPF in patients with diffuse lung diseases. In addition, they also have a promising future as therapeutics for LD. In this review, we focus on the importance of airway secretions in LD, the pivotal role of EVs from those secretions on their pathophysiology and their potential for biomarker discovery.

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N-Acetylcysteine Improves Inflammatory Response in COPD Patients by Regulating Th17/Treg Balance through Hypoxia Inducible Factor-1α Pathway

BioMed Research International ◽

10.1155/2021/6372128 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Xiaopeng Liu ◽

Zhixiong Hu ◽

Haiying Zhou

Keyword(s):

Hypoxia Inducible Factor ◽

Control Group ◽

Chronic Obstructive ◽

T Lymphocyte Subsets ◽

Obstructive Pulmonary Disease ◽

Hypoxia Inducible Factor 1Α ◽

Copd Patients ◽

New Diagnosis ◽

Serum Testing

Introduction. This study was aimed to investigate the effects of N-acetylcysteine (NAC) on chronic obstructive pulmonary disease (COPD) and the change of Th17/Treg cytokine imbalance. Material and Methods. A total of 121 patients with stable COPD at the stage of C or D were consecutively enrolled and randomly divided into 2 groups. Patients in the treatment group received NAC granules ( 0.2 g × 10 bags , 0.4 g each time, 3 times/d) for half a year. The control group was treated with the same amount of placebo therapy. The peripheral blood of the patient was collected and the cytokine, T lymphocyte subsets were detected. Results. We found the oral administration of NAC could regulate Th17/Treg balance to resist inflammation in COPD patients. Serum testing showed that the proportion of Treg in CD4+ T cells has increased and the Th17/Treg ratio has decreased during the NAC treatment. In vitro studies, we found that NAC regulated Th17/Treg balance through Hypoxia Inducible Factor-1α pathway. Conclusions. Our result could provide new diagnosis and treatment for elderly patients with COPD from the perspective of immunity ideas.

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Pulmonary Hypertension in Parenchymal Lung Disease

Pulmonary Medicine ◽

10.1155/2012/684781 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Iraklis Tsangaris ◽

Georgios Tsaknis ◽

Anastasia Anthi ◽

Stylianos E. Orfanos

Keyword(s):

Pulmonary Hypertension ◽

Lung Diseases ◽

Interstitial Lung Diseases ◽

Idiopathic Pulmonary Arterial Hypertension ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Diffuse Parenchymal Lung Diseases ◽

Pulmonary Arterial ◽

Parenchymal Lung Disease ◽

Parenchymal Lung

Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases.

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The Role of Lycopene in Chronic Lung Diseases

10.5772/intechopen.95468 ◽

2021 ◽

Author(s):

Emilio Balbuena ◽

Junrui Cheng ◽

Abdulkerim Eroglu

Keyword(s):

Lung Cancer ◽

Lung Diseases ◽

Protective Role ◽

In Vivo Studies ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Chronic Lung Diseases ◽

Bell Peppers

Lycopene, a naturally occurring non-provitamin A carotenoid pigment, is responsible for the red to pink colors in tomato, watermelon, red bell peppers, and pink guava. There are many health benefits attributed to lycopene including but not limited to its antioxidant activity. According to the American Lung Association’s State of Lung Cancer, lung cancer is still the leading cause of cancer death in the United States. Other chronic lung diseases such as asthma, emphysema, and chronic obstructive pulmonary disease are high prevalence. This chapter summarizes lycopene’s protective role against lung diseases in both in vitro and in vivo studies. While it has been demonstrated that circulating lycopene can be used as a biomarker for several lung diseases, further studies are warranted to establish that. We aim to provide insights into how lycopene can remedy for lung diseases, including lung cancer.

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Dexmedetomidine targets miR-146a and participates in the progress of chronic obstructive pulmonary disease in vivo and in vitro

Genes & Genomics ◽

10.1007/s13258-020-01019-2 ◽

2021 ◽

Author(s):

Na Li ◽

Shuangfeng Li ◽

Yehua Wu ◽

Lu Xiong ◽

Tiejun Li ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease

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The roles of exosomal miRNAs and lncRNAs in lung diseases

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-019-0080-7 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 19

Author(s):

Yang Li ◽

Zhengrong Yin ◽

Jinshuo Fan ◽

Siyu Zhang ◽

Weibing Yang

Keyword(s):

Lung Cancer ◽

Information Exchange ◽

Lung Diseases ◽

Cell Communication ◽

Diagnostic Methods ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Diagnostic Biomarkers ◽

Exosomal Mirnas ◽

New Ideas

Abstract An increasing number of studies have reported that exosomes released from various cells can serve as mediators of information exchange between different cells. With further exploration of exosome content, a more accurate molecular mechanism involved in the process of cell-to-cell communication has been revealed; specifically, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are shuttled by exosomes. In addition, exosomal miRNAs and lncRNAs may play vital roles in the pathogenesis of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), lung cancer, and asthma. Consequently, exosomal miRNAs and lncRNAs show promise as diagnostic biomarkers and therapeutic targets in several lung diseases. This review will summarize recent knowledge about the roles of exosomal miRNAs and lncRNAs in lung diseases, which has shed light on the discovery of novel diagnostic methods and treatments for these disorders. Because there is almost no published literature about exosomal lncRNAs in COPD, asthma, interstitial lung disease, or tuberculosis, we summarize the roles of exosomal lncRNAs only in lung cancer in the second section. This may inspire some new ideas for researchers who are interested in whether lncRNAs shuttled by exosomes may play roles in other lung diseases.

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A Comparison between Two Pathophysiologically Different yet Microbiologically Similar Lung Diseases: Cystic Fibrosis and Chronic Obstructive Pulmonary Disease

International Journal of Respiratory and Pulmonary Medicine ◽

10.23937/2378-3516/1410098 ◽

2018 ◽

Vol 5 (2) ◽

Cited By ~ 1

Author(s):

Fenker Daniel E ◽

McDaniel Cameron T ◽

Panmanee Warunya ◽

Panos Ralph J ◽

Sorscher Eric J ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Cystic Fibrosis ◽

Pulmonary Disease ◽

Lung Diseases ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease

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Cell therapy for lung disease

European Respiratory Review ◽

10.1183/16000617.0044-2017 ◽

2017 ◽

Vol 26 (144) ◽

pp. 170044 ◽

Cited By ~ 33

Author(s):

Sabine Geiger ◽

Daniela Hirsch ◽

Felix G. Hermann

Keyword(s):

Clinical Studies ◽

Therapeutic Approach ◽

Lung Diseases ◽

Distress Syndrome ◽

Treatment Options ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Cell Therapies ◽

Promising Therapeutic Approach ◽

Preclinical And Clinical Studies

Besides cancer and cardiovascular diseases, lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions no effective and curative treatment options are available. Cell therapies offer a novel therapeutic approach due to their inherent anti-inflammatory and anti-fibrotic properties. Mesenchymal stem/stromal cells (MSC) are the most studied cell product. Numerous preclinical studies demonstrate an improvement of disease-associated parameters after MSC administration in several lung disorders, including chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis. Furthermore, results from clinical studies using MSCs for the treatment of various lung diseases indicate that MSC treatment in these patients is safe. In this review we summarise the results of preclinical and clinical studies that indicate that MSCs are a promising therapeutic approach for the treatment of lung diseases. Nevertheless, further investigations are required.

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