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 Muscarinic M3 receptors on structural cells regulate cigarette smoke-induced neutrophilic airway inflammation in mice

2015 ◽  
Vol 308 (1) ◽  
pp. L96-L103 ◽  
Author(s):  
Loes E. M. Kistemaker ◽  
Ronald P. van Os ◽  
Albertina Dethmers-Ausema ◽  
I. Sophie T. Bos ◽  
Machteld N. Hylkema ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cigarette Smoke ◽  
Neutrophil Migration ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Chronic Obstructive ◽  
Wild Type ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Relative Contribution

Anticholinergics, blocking the muscarinic M3 receptor, are effective bronchodilators for patients with chronic obstructive pulmonary disease. Recent evidence from M3 receptor-deficient mice (M3R−/−) indicates that M3 receptors also regulate neutrophilic inflammation in response to cigarette smoke (CS). M3 receptors are present on almost all cell types, and in this study we investigated the relative contribution of M3 receptors on structural cells vs. inflammatory cells to CS-induced inflammation using bone marrow chimeric mice. Bone marrow chimeras (C56Bl/6 mice) were generated, and engraftment was confirmed after 10 wk. Thereafter, irradiated and nonirradiated control animals were exposed to CS or fresh air for four consecutive days. CS induced a significant increase in neutrophil numbers in nonirradiated and irradiated control animals (4- to 35-fold). Interestingly, wild-type animals receiving M3R−/− bone marrow showed a similar increase in neutrophil number (15-fold). In contrast, no increase in the number of neutrophils was observed in M3R−/− animals receiving wild-type bone marrow. The increase in keratinocyte-derived chemokine (KC) levels was similar in all smoke-exposed groups (2.5- to 5.0-fold). Microarray analysis revealed that fibrinogen-α and CD177, both involved in neutrophil migration, were downregulated in CS-exposed M3R−/− animals receiving wild-type bone marrow compared with CS-exposed wild-type animals, which was confirmed by RT-qPCR (1.6–2.5 fold). These findings indicate that the M3 receptor on structural cells plays a proinflammatory role in CS-induced neutrophilic inflammation, whereas the M3 receptor on inflammatory cells does not. This effect is probably not mediated via KC release, but may involve altered adhesion and transmigration of neutrophils via fibrinogen-α and CD177.

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 Signaling Control of Mucociliary Epithelia: Stem Cells, Cell Fates, and the Plasticity of Cell Identity in Development and Disease

2021 ◽  
pp. 1-18
Author(s):  
Peter Walentek
Keyword(s):  
Stem Cells ◽  
Mucociliary Clearance ◽  
Cell Types ◽  
Secretory Cells ◽  
Chronic Obstructive ◽  
Cell Identity ◽  
Obstructive Pulmonary Disease ◽  
Congenital Diseases ◽  
Inhaled Particles ◽  
Mucociliary Epithelia

Mucociliary epithelia are composed of multiciliated, secretory, and stem cells and line various organs in vertebrates such as the respiratory tract. By means of mucociliary clearance, those epithelia provide a first line of defense against inhaled particles and pathogens. Mucociliary clearance relies on the correct composition of cell types, that is, the proper balance of ciliated and secretory cells. A failure to generate and to maintain correct cell type composition and function results in impaired clearance and high risk to infections, such as in congenital diseases (e.g., ciliopathies) as well as in acquired diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). While it remains incompletely resolved how precisely cell types are specified and maintained in development and disease, many studies have revealed important mechanisms regarding the signaling control in mucociliary cell types in various species. Those studies not only provided insights into the signaling contribution to organ development and regeneration but also highlighted the remarkable plasticity of cell identity encountered in mucociliary maintenance, including frequent trans-differentiation events during homeostasis and specifically in disease. This review will summarize major findings and provide perspectives regarding the future of mucociliary research and the treatment of chronic airway diseases associated with tissue remodeling.

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.

Respiratory medicine

2014 ◽  
pp. 293-340
Author(s):  
Chantal Simon ◽  
Hazel Everitt ◽  
Françoise van Dorp ◽  
Matt Burkes
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Drug Treatment ◽  
Pulmonary Disease ◽  
Respiratory Disease ◽  
Asthma Management ◽  
Respiratory Medicine ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Acute Exacerbations

Breathlessness Cough Chest signs Other signs of respiratory disease Respiratory investigations Bronchodilators and steroids Asthma in adults Asthma management in practice Drug treatment of asthma Chronic obstructive pulmonary disease Management of COPD Acute exacerbations of COPD Lung cancer Colds and influenza Pneumonia in adults Tuberculosis...

scholarly journals Tai Chi Movements for Wellbeing – evaluation of a British Lung Foundation pilot

2019 ◽  
Vol 140 (3) ◽  
pp. 172-180 ◽  
Author(s):  
A Lewis ◽  
NS Hopkinson
Keyword(s):  
Respiratory Disease ◽  
Tai Chi ◽  
Exercise Intervention ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Assessment Test ◽  
Qualitative Feedback ◽  
Improve Exercise Capacity ◽  
The Uk

Aims: In breathless individuals with respiratory disease, pulmonary rehabilitation (PR) can improve exercise capacity, symptoms and ability to cope with their condition. However, access is often limited, and adherence can be poor. Thus, there is interest in developing alternative and complementary forms of exercise intervention and tai chi may be effective in this context. Method: The British Lung Foundation worked in collaboration with ‘Tai Chi Movements for Wellbeing’ Training to train leaders to run community-based tai chi groups in the UK. Leaders received funding to run 3 months of once-a-week classes consisting of a 12 movement sequence of tai chi. Participants completed a questionnaire survey to evaluate the service at the start of their first session and again after 3 months. Results: Ten tai chi groups recruited 128 participants, 65% women, mean (standard deviation (SD)) age 70.1 (7.4) years at baseline. Seventy individuals completed the follow-up questionnaire at 3 months. Participants demonstrated an improvement in Medical Research Council (MRC) Dyspnoea Score pre 3 (interquartile range (IQR) = 1.8), post 2 (IQR = 1), p = .013 and disease burden; chronic obstructive pulmonary disease (COPD) assessment test score pre 19.4 (8.7), post 17.9 (9.4), mean change –1.5 (confidence interval (CI): –2.89 to –0.127), p = .033. Those who completed the programme had a worse baseline COPD assessment test (CAT) score and were more likely to have participated in maintenance exercise previously. Qualitative feedback suggested that participants felt the classes had helped with breathlessness and relaxation. Conclusion: Establishing a tai chi for wellbeing programme for people with respiratory disease is feasible, with a reasonable level of compliance, and is perceived to be helpful by participants.

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