scholarly journals Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

2020 ◽  
Vol 21 (3) ◽  
pp. 851 ◽  
Author(s):  
Vincent D. Giacalone ◽  
Camilla Margaroli ◽  
Marcus A. Mall ◽  
Rabindra Tirouvanziam
Keyword(s):  
Immune Responses ◽  
Defense Mechanisms ◽  
Inflammatory Diseases ◽  
Primary Response ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Public Health Burden ◽  
Chronic Lung Diseases ◽  
New Concepts

Neutrophils have a prominent role in all human immune responses against any type of pathogen or stimulus. The lungs are a major neutrophil reservoir and neutrophilic inflammation is a primary response to both infectious and non-infectious challenges. While neutrophils are well known for their essential role in clearance of bacteria, they are also equipped with specific mechanisms to counter viruses and fungi. When these defense mechanisms become aberrantly activated in the absence of infection, this commonly results in debilitating chronic lung inflammation. Clearance of bacteria by phagocytosis is the hallmark role of neutrophils and has been studied extensively. New studies on neutrophil biology have revealed that this leukocyte subset is highly adaptable and fulfills diverse roles. Of special interest is how these adaptations can impact the outcome of an immune response in the lungs due to their potent capacity for clearing infection and causing damage to host tissue. The adaptability of neutrophils and their propensity to influence the outcome of immune responses implicates them as a much-needed target of future immunomodulatory therapies. This review highlights the recent advances elucidating the mechanisms of neutrophilic inflammation, with a focus on the lung environment due to the immense and growing public health burden of chronic lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), and acute lung inflammatory diseases such as transfusion-related acute lung injury (TRALI).

scholarly journals Neutrophilic Inflammation in the Immune Responses of Chronic Obstructive Pulmonary Disease: Lessons from Animal Models

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Gang Huang ◽  
Xu-Chen Xu ◽  
Jie-Sen Zhou ◽  
Zhou-Yang Li ◽  
Hai-Pin Chen ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Animal Models ◽  
Immune Responses ◽  
Pulmonary Disease ◽  
Whole Body ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Advantages And Disadvantages

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide, which is characterized by chronic bronchitis, destruction of small airways, and enlargement/disorganization of alveoli. It is generally accepted that the neutrophilic airway inflammation observed in the lungs of COPD patients is intrinsically linked to the tissue destruction and alveolar airspace enlargement, leading to disease progression. Animal models play an important role in studying the underlying mechanisms of COPD as they address questions involving integrated whole body responses. This review aims to summarize the current animal models of COPD, focusing on their advantages and disadvantages on immune responses and neutrophilic inflammation. Also, we propose a potential new animal model of COPD, which may mimic the most characteristics of human COPD pathogenesis, including persistent moderate-to-high levels of neutrophilic inflammation.

Toll-like receptor (TLR)-based networks regulate neutrophilic inflammation in respiratory disease

2007 ◽  
Vol 35 (6) ◽  
pp. 1492-1495 ◽  
Author(s):  
I. Sabroe ◽  
M.K.B. Whyte
Keyword(s):  
Respiratory Disease ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Tissue Cell ◽  
Chronic Obstructive ◽  
Toll Like Receptor ◽  
Microbial Infection ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Monocytes And Macrophages

The neutrophil is a crucial early defence against microbial infection, but neutrophilic inflammation can result in devastating acute and chronic inflammatory diseases. In the lungs, the neutrophil is a principal part of the pathology of the acute respiratory distress syndrome, and its activation may also be of substantial importance in chronic obstructive pulmonary disease and some forms of asthma. Induction of neutrophil recruitment in response to microbial attack requires activation of TLR (Toll-like receptor)-based signalling pathways and the concerted actions of multiple cell types, including sentinel cells such as monocytes and macrophages acting together with tissue cell types such as the epithelium or smooth-muscle cell. The present review describes some of these networks and the resulting potential for their targeting in respiratory disease.

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

scholarly journals Inhibition of ErbB kinase signalling promotes resolution of neutrophilic inflammation

2019 ◽  
Author(s):  
A. Rahman ◽  
K. M. Henry ◽  
K. D. Herman ◽  
A. A. R Thompson ◽  
H. M. Isles ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Human Neutrophils ◽  
Chronic Obstructive ◽  
Neutrophil Apoptosis ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Injury Model ◽  
Neutrophil Survival

AbstractNeutrophilic inflammation with prolonged neutrophil survival is common to many inflammatory conditions, including chronic obstructive pulmonary disease (COPD). There are few specific therapies that reverse neutrophilic inflammation, but uncovering mechanisms regulating neutrophil survival is likely to identify novel therapeutic targets. Screening of 367 kinase inhibitors in human neutrophils and a zebrafish tail fin injury model identified ErbBs as common targets of compounds that accelerated inflammation resolution. The ErbB inhibitors gefitinib, CP-724714, erbstatin and tyrphostin AG825 significantly accelerated apoptosis of human neutrophils, including neutrophils from people with COPD. Neutrophil apoptosis was also increased in Tyrphostin AG825 treated-zebrafishin vivo. Tyrphostin AG825 decreased peritoneal inflammation in zymosan-treated mice, and increased lung neutrophil apoptosis and macrophage efferocytosis in a murine acute lung injury model. Tyrphostin AG825 and knockdown ofegfraanderbb2by CRISPR/Cas9 reduced inflammation in zebrafish. Our work shows that inhibitors of ErbB kinases have therapeutic potential in neutrophilic inflammatory disease.

scholarly journals Asthma‐chronic obstructive pulmonary disease overlap: A clinical entity?

2020 ◽  
Vol 3 (1) ◽  
pp. 2-8
Author(s):  
Robert A. Wise
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Middle Age ◽  
Clinical Manifestations ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Normal Lung Function

Asthma and COPD are easily recognizable clinical entities in their characteristic presentations. Asthma is an early-onset disorder characterized by Type 2, eosinophil-predominant, inflammation of the airways and is associated with atopy. COPD presents in middle age and is characterized by neutrophilic inflammation of the airways and is associated with cigarette smoking or biomass fuel exposure. Between exacerbations, asthma typically has normal lung function whereas COPD has incompletely reversible lung function. Approximately one in five patients with either of these disorders will show some features of both COPD and Asthma. This overlap is far more common than can be accounted for by chance concurrence of two common diseases. There are likely genetic and environmental susceptibilities to both disorders, but there is no single pathobiological mechanism that identifies all such overlap patients. Most likely there are numerous predispositions that lead to Asthma-COPD overlap that may be grounded in early childhood or even pre-natal events. Thus, Asthma-COPD overlap is best considered a family of diseases with overlapping clinical manifestations. The future elucidation of these different pathways to Asthma-COPD overlap, in conjunction with highly targeted therapies will aid clinicians in treating these patients.

scholarly journals Iron and Sphingolipids as Common Players of (Mal)Adaptation to Hypoxia in Pulmonary Diseases

2020 ◽  
Vol 21 (1) ◽  
pp. 307 ◽  
Author(s):  
Sara Ottolenghi ◽  
Aida Zulueta ◽  
Anna Caretti
Keyword(s):  
High Altitude ◽  
Inflammatory Diseases ◽  
Physiological Adaptation ◽  
Adaptation To Hypoxia ◽  
Chronic Obstructive ◽  
Compensatory Response ◽  
Obstructive Pulmonary Disease ◽  
Pathological Conditions ◽  
High Altitude Pulmonary Edema ◽  
Sphingosine 1 Phosphate

Hypoxia, or lack of oxygen, can occur in both physiological (high altitude) and pathological conditions (respiratory diseases). In this narrative review, we introduce high altitude pulmonary edema (HAPE), acute respiratory distress syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), and Cystic Fibrosis (CF) as examples of maladaptation to hypoxia, and highlight some of the potential mechanisms influencing the prognosis of the affected patients. Among the specific pathways modulated in response to hypoxia, iron metabolism has been widely explored in recent years. Recent evidence emphasizes hepcidin as highly involved in the compensatory response to hypoxia in healthy subjects. A less investigated field in the adaptation to hypoxia is the sphingolipid (SPL) metabolism, especially through Ceramide and sphingosine 1 phosphate. Both individually and in concert, iron and SPL are active players of the (mal)adaptation to physiological hypoxia, which can result in the pathological HAPE. Our aim is to identify some pathways and/or markers involved in the physiological adaptation to low atmospheric pressures (high altitudes) that could be involved in pathological adaptation to hypoxia as it occurs in pulmonary inflammatory diseases. Hepcidin, Cer, S1P, and their interplay in hypoxia are raising growing interest both as prognostic factors and therapeutical targets.

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