Chemokine receptors and their therapeutic opportunities in diseased lung: Far beyond leukocyte trafficking

2015 ◽  
Vol 308 (7) ◽  
pp. L603-L618 ◽  
Author(s):  
Tereza Tomankova ◽  
Eva Kriegova ◽  
Mingyao Liu
Keyword(s):  
Lung Tissue ◽  
Chemokine Receptors ◽  
Lung Diseases ◽  
Immune Cell ◽  
Critical Role ◽  
Chronic Obstructive ◽  
Potential Contribution ◽  
Cell Trafficking ◽  
Obstructive Pulmonary Disease ◽  
Current State

Chemokine receptors and their chemokine ligands, key mediators of inflammatory and immune cell trafficking, are involved in the regulation of both physiological and pathological processes in the lung. The discovery that chemokine receptors/chemokines, typically expressed by inflammatory and immune cells, are also expressed in structural lung tissue cells suggests their role in mediating the restoration of lung tissue structure and functions. Thus, chemokine receptors/chemokines contribute not only to inflammatory and immune responses in the lung but also play a critical role in the regulation of lung tissue repair, regeneration, and remodeling. This review aims to summarize current state-of-the-art on chemokine receptors and their ligands in lung diseases such as chronic obstructive pulmonary disease, asthma/allergy, pulmonary fibrosis, acute lung injury, and lung infection. Furthermore, the therapeutic opportunities of chemokine receptors in aforementioned lung diseases are discussed. The review also aims to delineate the potential contribution of chemokine receptors to the processes leading to repair/regeneration of the lung tissue.

scholarly journals New Pharmacological Tools to Target Leukocyte Trafficking in Lung Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Kylie B. R. Belchamber ◽  
Michael J. Hughes ◽  
Daniella A. Spittle ◽  
Eloise M. Walker ◽  
Elizabeth Sapey
Keyword(s):  
Lung Disease ◽  
Immune Cells ◽  
Lung Diseases ◽  
Immune Cell ◽  
Current Evidence ◽  
Chronic Obstructive ◽  
Cellular Functions ◽  
Obstructive Pulmonary Disease ◽  
Microbial Invasion ◽  
Infection And Inflammation

Infection and inflammation of the lung results in the recruitment of non-resident immune cells, including neutrophils, eosinophils and monocytes. This swift response should ensure clearance of the threat and resolution of stimuli which drive inflammation. However, once the threat is subdued this influx of immune cells should be followed by clearance of recruited cells through apoptosis and subsequent efferocytosis, expectoration or retrograde migration back into the circulation. This cycle of cell recruitment, containment of threat and then clearance of immune cells and repair is held in exquisite balance to limit host damage. Advanced age is often associated with detrimental changes to the balance described above. Cellular functions are altered including a reduced ability to traffic accurately towards inflammation, a reduced ability to clear pathogens and sustained inflammation. These changes, seen with age, are heightened in lung disease, and most chronic and acute lung diseases are associated with an exaggerated influx of immune cells, such as neutrophils, to the airways as well as considerable inflammation. Indeed, across many lung diseases, pathogenesis and progression has been associated with the sustained presence of trafficking cells, with examples including chronic diseases such as Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis and acute infections such as Pneumonia and Pneumonitis. In these instances, there is evidence that dysfunctional and sustained recruitment of cells to the airways not only increases host damage but impairs the hosts ability to effectively respond to microbial invasion. Targeting leukocyte migration in these instances, to normalise cellular responses, has therapeutic promise. In this review we discuss the current evidence to support the trafficking cell as an immunotherapeutic target in lung disease, and which potential mechanisms or pathways have shown promise in early drug trials, with a focus on the neutrophil, as the quintessential trafficking immune cell.

scholarly journals Cellular senescence in the lung across the age spectrum

2019 ◽  
Vol 316 (5) ◽  
pp. L826-L842 ◽  
Author(s):  
Pavan Parikh ◽  
Sarah Wicher ◽  
Karl Khandalavala ◽  
Christina M. Pabelick ◽  
Rodney D. Britt ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Lung Diseases ◽  
Normal Lung ◽  
Future Research ◽  
Chronic Obstructive ◽  
Potential Contribution ◽  
Obstructive Pulmonary Disease ◽  
Paracrine Effects ◽  
Tissue Repair And Regeneration ◽  
Growth And Aging

Cellular senescence results in cell cycle arrest with secretion of cytokines, chemokines, growth factors, and remodeling proteins (senescence-associated secretory phenotype; SASP) that have autocrine and paracrine effects on the tissue microenvironment. SASP can promote remodeling, inflammation, infectious susceptibility, angiogenesis, and proliferation, while hindering tissue repair and regeneration. While the role of senescence and the contributions of senescent cells are increasingly recognized in the context of aging and a variety of disease states, relatively less is known regarding the portfolio and influences of senescent cells in normal lung growth and aging per se or in the induction or progression of lung diseases across the age spectrum such as bronchopulmonary dysplasia, asthma, chronic obstructive pulmonary disease, or pulmonary fibrosis. In this review, we introduce concepts of cellular senescence, the mechanisms involved in the induction of senescence, and the SASP portfolio that are relevant to lung cells, presenting the potential contribution of senescent cells and SASP to inflammation, hypercontractility, and remodeling/fibrosis: aspects critical to a range of lung diseases. The potential to blunt lung disease by targeting senescent cells using a novel class of drugs (senolytics) is discussed. Potential areas for future research on cellular senescence in the lung are identified.

scholarly journals The emerging role of myeloid-derived suppressor cells in lung diseases

2016 ◽  
Vol 47 (3) ◽  
pp. 967-977 ◽  
Author(s):  
Saeed Kolahian ◽  
Hasan Halit Öz ◽  
Benyuan Zhou ◽  
Christoph M. Griessinger ◽  
Nikolaus Rieber ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Suppressor Cells ◽  
Innate Immune ◽  
Chronic Obstructive ◽  
Potential Contribution ◽  
Innate Immune Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Obstructive Pulmonary Disease ◽  
Cell Responses

Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterised by their potential to control T-cell responses and to dampen inflammation. While the role of MDSCs in cancer has been studied in depth, our understanding of their relevance for infectious and inflammatory disease conditions has just begun to evolve. Recent studies highlight an emerging and complex role for MDSCs in pulmonary diseases. In this review, we discuss the potential contribution of MDSCs as biomarkers and therapeutic targets in lung diseases, particularly lung cancer, tuberculosis, chronic obstructive pulmonary disease, asthma and cystic fibrosis.

scholarly journals The roles of exosomal miRNAs and lncRNAs in lung diseases

2019 ◽  
Vol 4 (1) ◽  
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.

scholarly journals Cell therapy for lung disease

2017 ◽  
Vol 26 (144) ◽  
pp. 170044 ◽  
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.

scholarly journals Chronic Obstructive Pulmonary Disease: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

2014 ◽  
Vol 11 (Supplement 3) ◽  
pp. S154-S160 ◽  
Author(s):  
M. Bradley Drummond ◽  
A. Sonia Buist ◽  
James D. Crapo ◽  
Robert A. Wise ◽  
Stephen I. Rennard
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Primary Prevention ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases
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