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Inflamation of COPD

Kim Hoenderdos, Katharine M Lodge, Robert A Hirst, Cheng Chen, Stefano G C Palazzo, Annette Emerenciana, Charlotte Summers, Adri Angyal, Linsey Porter, Jatinder K Juss, Christopher O'Callaghan, Edwin R Chilvers, Alison M Condliffe
BACKGROUND: The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. METHODS AND RESULTS: Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents...
November 2016: Thorax
Koshika Yadava, Paul Bollyky, Melissa A Lawson
Tertiary lymphoid follicles (TLFs) can develop in the respiratory tract in response to infections or chronic inflammation. However, their functional relevance remains unclear because they are implicated in both protective and pathological responses. In contrast to homeostatic conditions, external antigens and damage to the lung tissue may drive TLF formation in inflamed lungs, and once established, the presence of pulmonary TLFs may signal the progression of chronic lung disease. This novel concept will be discussed in light of recent work in chronic obstructive pulmonary disease and how changes in the pulmonary microbiota may drive and direct TLF formation and function...
November 2016: Immunology
Jonathan S Silver, Jennifer Kearley, Alan M Copenhaver, Caroline Sanden, Michiko Mori, Li Yu, Gretchen Harms Pritchard, Aaron A Berlin, Christopher A Hunter, Russell Bowler, Jonas S Erjefalt, Roland Kolbeck, Alison A Humbles
Innate lymphoid cells (ILCs) are critical mediators of mucosal immunity, and group 1 ILCs (ILC1 cells) and group 3 ILCs (ILC3 cells) have been shown to be functionally plastic. Here we found that group 2 ILCs (ILC2 cells) also exhibited phenotypic plasticity in response to infectious or noxious agents, characterized by substantially lower expression of the transcription factor GATA-3 and a concomitant switch to being ILC1 cells that produced interferon-γ (IFN-γ). Interleukin 12 (IL-12) and IL-18 regulated this conversion, and during viral infection, ILC2 cells clustered within inflamed areas and acquired an ILC1-like phenotype...
June 2016: Nature Immunology
Anna Caretti, Riccardo Torelli, Federica Perdoni, Monica Falleni, Delfina Tosi, Aida Zulueta, Josefina Casas, Maurizio Sanguinetti, Riccardo Ghidoni, Elisa Borghi, Paola Signorelli
BACKGROUND: Fungal infections develop in pulmonary chronic inflammatory diseases such as asthma, Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF). The available antifungal drugs may fail to eradicate fungal pathogens, that can invade the lungs and vessels and spread by systemic circulation taking advantage of defective lung immunity. An increased rate of sphingolipid de novo synthesis, leading to ceramide accumulation, was demonstrated in CF and COPD inflamed lungs...
June 2016: Biochimica et Biophysica Acta
Gilda Varricchi, Diego Bagnasco, Francesco Borriello, Enrico Heffler, Giorgio W Canonica
PURPOSE OF REVIEW: Human eosinophils were first identified and named by Paul Ehrlich in 1879 on the basis of the cell's granular uptake of eosin. Although eosinophils represent approximately 1% of peripheral blood leukocytes, they have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophils and their mediators are critical effectors to asthma and eosinophilic granulomatosis with polyangiitis (EGPA). Eosinophils are equipped with a large number of cell-surface receptors and produce specific cytokines and chemokines...
April 2016: Current Opinion in Allergy and Clinical Immunology
Koshika Yadava, Céline Pattaroni, Anke K Sichelstiel, Aurélien Trompette, Eva S Gollwitzer, Olawale Salami, Christophe von Garnier, Laurent P Nicod, Benjamin J Marsland
RATIONALE: Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. OBJECTIVES: To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic)...
May 1, 2016: American Journal of Respiratory and Critical Care Medicine
P Santus, D Radovanovic, P Paggiaro, A Papi, A Sanduzzi, N Scichilone, F Braido
Long-acting β2-adrenoceptor agonists, formoterol and salmeterol, represent a milestone in the treatments of chronic obstructive lung diseases. Although no specific indications concerning the choice of one molecule rather than another are provided by asthma and COPD guidelines, they present different pharmacological properties resulting in distinct clinical employment possibilities. In particular, salmeterol has a low intrinsic efficacy working as a partial receptor agonist, while formoterol is a full agonist with high intrinsic efficacy...
July 2015: European Journal of Internal Medicine
Amanda R Lever, Hyoungshin Park, Thomas J Mulhern, George R Jackson, James C Comolli, Jeffrey T Borenstein, Patrick J Hayden, Rachelle Prantil-Baun
Respiratory viruses invade the upper airway of the lung, triggering a potent immune response that often exacerbates preexisting conditions such as asthma and COPD. Poly(I:C) is a synthetic analog of viral dsRNA that induces the characteristic inflammatory response associated with viral infection, such as loss of epithelial integrity, and increased production of mucus and inflammatory cytokines. Here, we explore the mechanistic responses to poly(I:C) in a well-defined primary normal human bronchial epithelial (NHBE) model that recapitulates in vivo functions and responses...
April 2015: Physiological Reports
Steven Bozinovski, Desiree Anthony, Ross Vlahos
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition that is associated with irreversible airflow obstruction as a consequence of small airways disease, excessive mucus production and emphysema. Paradoxically, excessive inflammation fails to control microbial pathogens that not only colonise COPD airways, but also trigger acute exacerbations, which markedly increase inflammation underlying host tissue damage. Excessive production of leukocyte mobilising cytokines such as CXCL8 (IL-8) and leukotriene B4 (LTB4) in response to environmental stimuli (cigarette smoke and microbial products) are thought to maintain chronic inflammation, in conjunction with inefficient macrophage clearance of microbes and apoptotic neutrophils...
November 2014: Journal of Thoracic Disease
Daisy J A Janssen, Hana Müllerova, Alvar Agusti, Julie C Yates, Ruth Tal-Singer, Stephen I Rennard, Jørgen Vestbo, Emiel F M Wouters
BACKGROUND: Depression is highly prevalent among patients with Chronic Obstructive Pulmonary Disease (COPD). The relationship of depression with systemic inflammation in COPD remains unknown. The objective of this observational study was to compare depression scores at baseline and after 36 months follow-up between COPD patients with persistent systemic inflammation (PSI) and never inflamed patients (NI) in the ECLIPSE cohort. METHODS: The ECLIPSE study included 2164 COPD patients...
November 2014: Respiratory Medicine
Banu Boyuk, Eda C Guzel, Hande Atalay, Savas Guzel, Levent C Mutlu, Volkan Kucukyalçin
BACKGROUND AND AIMS: Chronic inflammation of the lung is a characteristic finding in chronic obstructive pulmonary disease (COPD). The protein chemerin has been identified in inflammatory fluid and in inflamed tissues. This study aimed to determine the association between serum chemerin levels and the severity of COPD. METHODS: Forty-three COPD patients and 38 healthy subjects were enrolled in this study. Fasting plasma samples were obtained from the patient and the control group...
October 2015: Clinical Respiratory Journal
Masoumeh E Givi, Michael J Peck, Louis Boon, Esmaeil Mortaz
Chronic Obstructive Pulmonary Disease (COPD) is an important lung and airway disease which affects the lives of around 200 million people worldwide. The pathological hallmark of COPD is emphysema and bronchiolitis and is based on the inflammatory response of the innate and adaptive immune system to the inhalation of toxic particles and gases. The inflamed airways of COPD patients contain several inflammatory cells including neutrophils, macrophages, T lymphocytes, and dendritic cells (DC). The potential role of DCs as mediators of inflammation in the airways of smokers and COPD patients is poorly understood...
December 5, 2013: European Journal of Pharmacology
John A Marwick, David A Dorward, Christopher D Lucas, Katie O Jones, Tara A Sheldrake, Sarah Fox, Carol Ward, Joanna Murray, Mairi Brittan, Nik Hirani, Rodger Duffin, Ian Dransfield, Christopher Haslett, Adriano G Rossi
GCs are highly effective in treating a wide range of inflammatory diseases but are limited in their ability to control neutrophilic lung inflammation in conditions such as COPD. Neutrophil apoptosis, a central feature of inflammation resolution, is delayed in response to microenvironmental cues, such as hypoxia and inflammatory cytokines, present at inflamed sites. GCs delay neutrophil apoptosis in vitro, and this may therefore limit the ability of GCs to control neutrophilic inflammation. This study assesses the effect GCs have on hypoxia- and inflammatory cytokine-induced neutrophil survival...
December 2013: Journal of Leukocyte Biology
Steven Bozinovski, Desiree Anthony, Gary P Anderson, Louis B Irving, Bruce D Levy, Ross Vlahos
Neutrophilic inflammation persists in COPD despite best current therapies and it is particularly resistant to inhaled glucocorticosteroids. Persistent neutrophil activation not only contributes to matrix breakdown, but can maintain inflammation through the release of endogenous damage associated molecule patterns (DAMPs). Inhibiting excessive neutrophilic inflammation is challenging as many pathogen recognition receptors can initiate migration and the targeting of downstream signaling molecules may compromise essential host defense mechanisms...
December 2013: Pharmacology & Therapeutics
Hasan Bayram, Fusun Fakili, Bülent Gögebakan, Recep Bayraktar, Serdar Oztuzcu, Oner Dikensoy, Kian Fan Chung
Patients with chronic airway diseases may be more susceptible to adverse effects of air pollutants including diesel exhaust particles (DEP). We investigated effects of foetal calf serum (FCS) on DEP-induced changes in airway epithelial cell apoptosis and inflammation. DEP (50-200 μg/ml) increased A549 cell viability in the absence of FCS. In the presence of 3.3%FCS, DEP (50-400 μg/ml) decreased A549 cell viability. N-acetylcysteine (NAC, 33 mM) and the c-jun N-terminal kinase (JNK) inhibitor (SP600125, 33 μM) further decreased the viability in the presence of DEP (200 μg/ml) and 3...
April 26, 2013: Toxicology Letters
Alvar Agustí, Lisa D Edwards, Stephen I Rennard, William MacNee, Ruth Tal-Singer, Bruce E Miller, Jørgen Vestbo, David A Lomas, Peter M A Calverley, Emiel Wouters, Courtney Crim, Julie C Yates, Edwin K Silverman, Harvey O Coxson, Per Bakke, Ruth J Mayer, Bartolome Celli
BACKGROUND: Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552). METHODS AND FINDINGS: Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years...
2012: PloS One
Masoumeh Ezzati Givi, Frank A Redegeld, Gert Folkerts, Esmaeil Mortaz
COPD (Chronic Obstructive Pulmonary Disease) is an important lung and airway disease which affects the lives of around 200 million people worldwide with an increasing incidence particularly in developing countries. The pathogenesis of COPD is based on the innate and adaptive inflammatory immune response to the inhalation of toxic particles and gases. Although cigarette smoking is the primary cause of this inflammation, many other environmental and occupational exposures contribute to the pathology of COPD. The immune inflammatory changes associated with COPD are linked to a tissue repair and remodeling process that increases mucus production and causes emphysematous destruction of the gas-exchanging surface of the lung...
2012: Current Pharmaceutical Design
Matthew J Loza, Rosemary Watt, Frédéric Baribaud, Elliot S Barnathan, Stephen I Rennard
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers. Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial. This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation...
2012: Respiratory Research
Anna Willems-Widyastuti, Vijay K T Alagappan, Uday Arulmani, Bart M Vanaudenaerde, Willem I de Boer, Wolter J Mooi, Geert M Verleden, Hari S Sharma
Increase in size and number of bronchial blood vessels as well as hyperaemia are factors that contribute to airway wall remodelling in patients with chronic airway diseases, such as asthma and chronic obstructive pulmonary diseases (COPD). Expression of transforming growth factor beta 1 (TGF-beta 1), a multifunctional cytokine as well as vascular endothelial growth factor (VEGF), a key angiogenic molecule, has been shown in the inflammed airways in patients with chronic airway diseases. TGF-beta 1 has been implicated in the regulation of extracellular matrix, leading to airway remodelling in patients with chronic airway diseases...
August 2011: Indian Journal of Biochemistry & Biophysics
Martina Kvist Reimer, Charlotte Brange, Alexander Rosendahl
CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD...
December 2011: Clinical and Vaccine Immunology: CVI
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