oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats
Agnès Roulet, Lucie Armand, Maylis Dagouassat, Fran?oise Rogerieux, Angélique Simon-Deckers, Esther Belade, Jeanne Van Nhieu, Sophie Lanone, Jean-Claude Pairon, Ghislaine Lacroix, Jorge Boczkowski
BMC Pulmonary Medicine , 2012, DOI: 10.1186/1471-2466-12-38
Abstract: On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg?1 pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and 500?μg) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1β (IL-1β), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry.TiO2 NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1β and macrophage MMP-12 expression and induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema.TiO2 and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages.Pulmonary emphysema is a chronic degenerative lung disease characterized by an imbalance in alveolar destruction and repair that results in progressive destruction of pulmonary alveoli and chronic respiratory failure [1]. Pulmonary emphysema is one of the components of chronic obstructive pulmonary disease (COPD), a frequent condition with a worldwide prevalence of more than 10% in men older than 40?years. The prevalence and mortality of COPD are predicted to further increase in the next decades [2]. Different processes are involved in alveolar destruction in emphysema, particularly excess of protease expr
IL-17RA Is Required for CCL2 Expression, Macrophage Recruitment, and Emphysema in Response to Cigarette Smoke  [PDF]
Kong Chen, Derek A. Pociask, Jeremy P. McAleer, Yvonne R. Chan, John F. Alcorn, James L. Kreindler, Matthew R. Keyser, Steven D. Shapiro, A. McGarry Houghton, Jay K. Kolls, Mingquan Zheng
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0020333
Abstract: Chronic Obstructive Pulmonary Disease (COPD) is characterized by airspace enlargement and peribronchial lymphoid follicles; however, the immunological mechanisms leading to these pathologic changes remain undefined. Here we show that cigarette smoke is a selective adjuvant that augments in vitro and in vivo Th17, but not Th1, cell differentiation via the aryl hydrocarbon receptor. Smoke exposed IL-17RA?/? mice failed to induce CCL2 and MMP12 compared to WT mice. Remarkably, in contrast to WT mice, IL-17RA?/? mice failed to develop emphysema after 6 months of cigarette smoke exposure. Taken together, these data demonstrate that cigarette smoke is a potent Th17 adjuvant and that IL-17RA signaling is required for chemokine expression necessary for MMP12 induction and tissue emphysema.
Defective Lung Macrophage Function in Lung Cancer±Chronic Obstructive Pulmonary Disease (COPD/Emphysema)-Mediated by Cancer Cell Production of PGE2?  [PDF]
Francis C. Dehle, Violet R. Mukaro, Craig Jurisevic, David Moffat, Jessica Ahern, Greg Hodge, Hubertus Jersmann, Paul N. Reynolds, Sandra Hodge
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061573
Abstract: In chronic obstructive pulmonary disease (COPD/emphysema) we have shown a reduced ability of lung and alveolar (AM) macrophages to phagocytose apoptotic cells (defective ‘efferocytosis’), associated with evidence of secondary cellular necrosis and a resultant inflammatory response in the airway. It is unknown whether this defect is present in cancer (no COPD) and if so, whether this results from soluble mediators produced by cancer cells. We investigated efferocytosis in AM (26 controls, 15 healthy smokers, 37 COPD, 20 COPD+ non small cell lung cancer (NSCLC) and 8 patients with NSCLC without COPD) and tumor and tumor-free lung tissue macrophages (21 NSCLC with/13 without COPD). To investigate the effects of soluble mediators produced by lung cancer cells we then treated AM or U937 macrophages with cancer cell line supernatant and assessed their efferocytosis ability. We qualitatively identified Arachidonic Acid (AA) metabolites in cancer cells by LC-ESI-MSMS, and assessed the effects of COX inhibition (using indomethacin) on efferocytosis. Decreased efferocytosis was noted in all cancer/COPD groups in all compartments. Conditioned media from cancer cell cultures decreased the efferocytosis ability of both AM and U937 macrophages with the most pronounced effects occurring with supernatant from SCLC (an aggressive lung cancer type). AA metabolites identified in cancer cells included PGE2. The inhibitory effect of PGE2 on efferocytosis, and the involvement of the COX-2 pathway were shown. Efferocytosis is decreased in COPD/emphysema and lung cancer; the latter at least partially a result of inhibition by soluble mediators produced by cancer cells that include PGE2.
Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation  [PDF]
Naoya Tanabe, Yuma Hoshino, Satoshi Marumo, Hirofumi Kiyokawa, Susumu Sato, Daisuke Kinose, Kazuko Uno, Shigeo Muro, Toyohiro Hirai, Junji Yodoi, Michiaki Mishima
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079016
Abstract: Background Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression. However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established. Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema. We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms. Results Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity. Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice. Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice. Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression. Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS. Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated. Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1. Conclusion Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression. Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation.
Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice
Lars Knudsen, Matthias Ochs, Rosemarie MacKay, Paul Townsend, Roona Deb, Christian Mühlfeld, Joachim Richter, Fabian Gilbert, Samuel Hawgood, Kenneth Reid, Howard Clark
Respiratory Research , 2007, DOI: 10.1186/1465-9921-8-70
Abstract: SP-D knock-out mice, aged 3 weeks, 6 weeks and 9 weeks were treated with rfhSP-D for 9, 6 and 3 weeks, respectively. All mice were sacrificed at age 12 weeks and compared to both PBS treated SP-D deficient and wild-type groups. Lung structure was quantified by design-based stereology at the light and electron microscopic level. Emphasis was put on quantification of emphysema, type II cell changes and intracellular surfactant. Data were analysed with two sided non-parametric Mann-Whitney U-test.After 3 weeks of treatment, alveolar number was higher and mean alveolar size was smaller compared to saline-treated SP-D knock-out controls. There was no significant difference concerning these indices of pulmonary emphysema within rfhSP-D treated groups. Type II cell number and size were smaller as a consequence of treatment. The total volume of lamellar bodies per type II cell and per lung was smaller after 6 weeks of treatment.Treatment of SP-D deficient mice with rfhSP-D leads to a reduction in the degree of emphysema and a correction of type II cell hyperplasia and hypertrophy. This supports the concept that rfhSP-D might become a therapeutic option in diseases that are characterized by decreased SP-D levels in the lung.Pulmonary emphysema or COPD is a common disease for which there is currently no effective therapy. The WHO estimates that COPD is the fifth leading cause of death worldwide (WHO world health report 2002) and the prevalence and mortality are expected to increase in the coming decades [1]. Several studies demonstrated, that surfactant protein D (SP-D) levels are diminished in the lung of smokers or cystic fibrosis patients [2-5]. Another study identified COPD susceptibility-alleles in the gene-location of the surfactant proteins, suggesting their role in the pathogenesis of COPD [6]. SP-D, along with surfactant protein A (SP-A) belong to the collectin family of mammalian C-type lectins and are known to be important innate host defense molecules at mucosal s
Quantification of Lung Damage in an Elastase-Induced Mouse Model of Emphysema  [PDF]
Arrate Mu?oz-Barrutia,Mario Ceresa,Xabier Artaechevarria,Luis M. Montuenga,Carlos Ortiz-de-Solorzano
International Journal of Biomedical Imaging , 2012, DOI: 10.1155/2012/734734
Abstract: Objective. To define the sensitivity of microcomputed tomography- (micro-CT-) derived descriptors for the quantification of lung damage caused by elastase instillation. Materials and Methods. The lungs of 30 elastase treated and 30 control A/J mice were analyzed 1, 6, 12, and 24 hours and 7 and 17 days after elastase instillation using (i) breath-hold-gated micro-CT, (ii) pulmonary function tests (PFTs), (iii) RT-PCR for RNA cytokine expression, and (iv) histomorphometry. For the latter, an automatic, parallel software toolset was implemented that computes the airspace enlargement descriptors: mean linear intercept and weighted means of airspace diameters ( , , and ). A Support Vector Classifier was trained and tested based on three nonhistological descriptors using as ground truth. Results. detected statistically significant differences between the groups at all time points. Furthermore, at 1 hour (24 hours) was significantly lower than at 24 hours (7 days). The classifier trained on the micro-CT-derived descriptors achieves an area under the curve (AUC) of 0.95 well above the others (PFTS AUC = 0.71; cytokine AUC = 0.88). Conclusion. Micro-CT-derived descriptors are more sensitive than the other methods compared, to detect in vivo early signs of the disease. 1. Introduction Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease. Traditionally, two phenotypes of COPD have been described: obstructive bronchitis and pulmonary emphysema. Because of current smoking trends and progressive aging of the world population, an increase in COPD prevalence and related mortality is expected in the coming decades [1]. Emphysema is defined pathologically as the permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls, without obvious fibrosis [2, 3]. At the molecular level, emphysema is an inflammatory-driven process caused by the enzymatic destruction of lung elastin and collagen by neutrophil and macrophage elastase [4]. The process is in most cases induced by cigarette smoking [5]. Animal models are key tools to study the disease. Probably the most widely extended one is the mouse model of elastase-induced emphysema, due to its simplicity and low cost [6]. Efficient and sensitive quantification of the injury is needed for the characterization of the disease and the assessment of therapeutic interventions on this model. In this paper, we describe efficient and sensitive methods to quantify histologically airspace enlargement ex vivo. This can in turn be used as an appropriate
The role of collagenase in emphysema
Robert Foronjy, Jeanine D'Armiento
Respiratory Research , 2001, DOI: 10.1186/rr85
Abstract: Emphysema is a common, debilitating pulmonary condition, the impact of which is felt worldwide, placing an enormous economic strain on international health care infrastructures. In the UK, data from 1996 indicate that the medical cost of chronic obstructive pulmonary disease (COPD) was approximately £846 million or about £1154 per person per year [1]. In the USA, over 106,000 people die from COPD yearly making it the fourth leading cause of death nationwide [2]. Moreover, while death rates for heart disease and stroke have declined by roughly 50% over the past 30 years, the death rate for COPD has risen by 71% [2]. In 1993, it was estimated that 14.7 billion dollars were spent in the USA on direct COPD-related health care expenditures, costing roughly the equivalent of £764 per person per year [1]. As the life expectancy of the populations of industrialized nations continues to increase, it is certain that the costs of emphysema in terms of lives lost and strains on limited health care resources will continue to grow.In light of these statistics on the global impact of this disease, it is surprising to realize that even the basic pathophysiology of emphysema is still being debated. While it is clearly established that cigarette smoke is the principal cause of emphysema, the mechanism by which cigarette smoke exposure leads to the destruction of lung architecture seen in emphysema is controversial. Elastin is an important component of the extracellular matrix (ECM) that is believed to confer upon the lung the resilience needed to undergo repetitive physiologic stress. For over 30 years, the leading hypothesis has been that emphysema resulted from an elastase/anti-elastase imbalance. This theory was formulated after it was noted that smokers with a congenital deficiency of alpha-1-antitrypsin (a1-AT) had an excessive incidence of emphysema [3]. Given the increased neutrophil content seen in the lungs of smokers and the fact that a1-AT inactivates neutrophil elastase,
Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?
An I D'hulst, Tania Maes, Ken R Bracke, Ingel K Demedts, Kurt G Tournoy, Guy F Joos, Guy G Brusselle
Respiratory Research , 2005, DOI: 10.1186/1465-9921-6-147
Abstract: In this study, wild type Balb/c mice and immunodeficient scid mice – which lack functional B- and T-cells – were exposed to mainstream cigarette smoke (CS) for 5 weeks or 6 months.Subacute CS-exposure for 5 weeks significantly increased innate inflammatory cells (neutrophils, macrophages and dendritic cells) in the bronchoalveolar lavage (BAL) fluid of wild type mice and scid mice, which correlated with the CS-induced upregulation of the chemokines Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein-3α and KC (= mouse Interleukin-8). Chronic CS-exposure for 6 months significantly increased the number of neutrophils, macrophages, dendritic cells, CD4+ and CD8+ T-lymphocytes in BAL fluid and lungs of wild type mice compared to air-exposed littermates, and augmented the size and number of peribronchial lymphoid follicles. In contrast, neither B-lymphocytes, nor T-lymphocytes, nor lymphoid follicles could be discerned in the lungs of air- or CS-exposed scid mice. Importantly, chronic CS-exposure induced pulmonary emphysema in both wild type animals and scid mice, as evidenced by a significant increase in the mean linear intercept and the destructive index of CS-exposed versus air-exposed animals. The CS-induced emphysema was associated with increased mRNA expression of matrix metalloproteinase-12 in the lungs and increased protein levels of Tumor Necrosis Factor-α in the BAL fluid of CS-exposed Balb/c and scid mice compared to air-exposed littermates.This study suggests that the adaptive immune system is not required per se to develop pulmonary emphysema in response to chronic CS-exposure, since emphysema can be induced in scid mice, which lack lymphoid follicles as well as functional B- and T-cells.Chronic obstructive pulmonary disease (COPD) is currently listed as the fifth leading cause of death in the world, and is also an important cause of chronic disability and permanent impairment, representing a major economic and social burden worldwide [1,2]. COPD
Centrilobular emphysema combined with pulmonary fibrosis results in improved survival
Nevins W Todd, Jean Jeudy, Sachin Lavania, Teri J Franks, Jeffrey R Galvin, Janaki Deepak, Edward J Britt, Sergei P Atamas
Fibrogenesis & Tissue Repair , 2011, DOI: 10.1186/1755-1536-4-6
Abstract: Based on the numerical emphysema score, patients were classified into those having no emphysema (n = 48), trivial emphysema (n = 26) or advanced emphysema (n = 28). Patients with advanced emphysema had a significantly higher amount of smoking in pack/years than patients with no emphysema or trivial emphysema (P < 0.0001). Median survival [1st, 3rd quartiles] of patients with advanced emphysema was 63 [36, 82] months compared to 29 [18, 49] months in patients without emphysema and 32 [19, 48] months in patients with trivial emphysema (P < 0.001). Median forced vital capacity (FVC) and total lung capacity (TLC) were higher in the advanced emphysema group compared to patients with no emphysema (P < 0.01 and P < 0.001, respectively), whereas median DLCO did not differ among groups and was overall low. Within the advanced emphysema group (n = 28), further characterization of the type of emphysema was performed and, within these subgroups of patients, survival was 75 [58, 85] months for patients with centrilobular emphysema, 75 [48, 85] months for patients with mixed centrilobular/paraseptal emphysema, and 24 [22, 35] months for patients with paraseptal emphysema (P < 0.01). Patients with advanced paraseptal emphysema had similar survival times to patients without emphysema.Patients with pulmonary fibrosis combined with advanced centrilobular or mixed emphysema have an improved survival compared with patients with pulmonary fibrosis without emphysema, with trivial emphysema or with advanced paraseptal emphysema.Pulmonary fibrosis is a major component of various diffuse parenchymal lung diseases, including idiopathic pulmonary fibrosis (IPF) and other forms of idiopathic interstitial pneumonia. Pulmonary fibrosis results in substantial morbidity and mortality and therapies have been uniformly poorly effective [1,2].Histological changes in the lungs of patients with IPF show usual interstitial pneumonia (UIP), a pattern of fibrosis characterized by fibroblastic foci and exc
Alveolar fractal box dimension inversely correlates with mean linear intercept in mice with elastase-induced emphysema
Andersen MP, Parham AR, Waldrep JC, McKenzie WN, Dhand R
International Journal of Chronic Obstructive Pulmonary Disease , 2012, DOI: http://dx.doi.org/10.2147/COPD.S26493
Abstract: lveolar fractal box dimension inversely correlates with mean linear intercept in mice with elastase-induced emphysema Original Research (1638) Total Article Views Authors: Andersen MP, Parham AR, Waldrep JC, McKenzie WN, Dhand R Published Date March 2012 Volume 2012:7 Pages 235 - 243 DOI: http://dx.doi.org/10.2147/COPD.S26493 Received: 23 September 2011 Accepted: 01 November 2011 Published: 27 March 2012 Mary P Andersen1, A Read Parham1, J Clifford Waldrep1,2, Wayland N McKenzie1, Rajiv Dhand1,2 1Division of Pulmonary, Critical Care, and Environmental Medicine, Department of Internal Medicine, University of Missouri, 2Research Services, Harry S Truman Memorial VA Hospital, Columbia, MO, USA Rationale: A widely applicable model of emphysema that allows efficient and sensitive quantification of injury is needed to compare potential therapies. Objectives: To establish such a model, we studied the relationship between elastase dose and the severity of emphysema in female C57BL/6J mice. We compared alveolar fractal box dimension (DB), a new measure which is an assessment of the complexity of the tissue, with mean linear intercept (Lm), which is commonly used to estimate airspace size, for sensitivity and efficiency of measurement. Methods: Emphysema was induced in female C57BL/6J mice by administering increasing intratracheal doses of porcine pancreatic elastase (PPE). Changes in morphology and static lung compliance (CL) were examined 21 days later. Correlation of DB with Lm was determined in histological sections of lungs exposed to PPE. The inverse relationship between DB and Lm was supported by examining similar morphological sections from another experiment where the development of emphysema was studied 1 to 3 weeks after instillation of human neutrophil elastase (HNE). Results: Lm increased with PPE dose in a sigmoidal curve. CL increased after 80 or 120 U/kg body weight (P < 0.05), but not after 40 U/kg, compared with the control. DB progressively declined from 1.66 ± 0.002 (standard error of the mean) in controls, to 1.47 ± 0.006 after 120 U PPE/kg (P < 0.0001). After PPE or HNE instillation, DB was inversely related to Lm (R = –0.95, P < 0.0001 and R = –0.84, P = 0.01, respectively), with a more negative slope of the relationship using HNE (P < 0.0001). Conclusion: Intratracheal instillation of increasing doses of PPE yields a scale of progression from mild to severe emphysema. DB correlates inversely with Lm after instillation of either PPE or HNE and yields a rapid, sensitive measure of emphysema after elastase instillation.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.