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American Journal of Physiology. Lung Cellular and Molecular Physiology

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https://www.readbyqxmd.com/read/27913427/intermittent-hypoxia-during-recovery-from-neonatal-hyperoxic-lung-injury-causes-long-term-impairment-of-alveolar-development-a-new-rat-model-of-bpd
#1
Anastasiya Mankouski, Crystal Kantores, Mathew J Wong, Julijana Ivanovska, Amish Jain, Eric J Benner, Stanley N Mason, A Keith Tanswell, Richard L Auten, Robert P Jankov
Bronchopulmonary dysplasia (BPD) is a chronic lung injury characterized by impaired alveologenesis that may persist into adulthood. Rat models of BPD using varying degrees of hyperoxia to produce injury either cause early mortality or spontaneously recover following removal of the inciting stimulus, thus limiting clinical relevance. We sought to refine an established rat model induced by exposure to 60% O2 from birth by following hyperoxia with intermittent hypoxia (IH). Rats exposed from birth to air or 60% O2 until day 14 were recovered in air with or without IH (FiO2 = 0...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913426/depletion-of-circulating-monocytes-suppresses-il-17-and-hmgb1-expression-in-mice-with-lps-induced-acute-lung-injury
#2
Zhilong Jiang, Qianlin Zhou, Chenlin Gu, Dandan Li, Lei Zhu
Acute lung injury/Acute Respiratory distress syndrome (ALI/ARDS) is an important cause of mortality in critically ill patients. Macrophages play an important role in the pathogenesis of ALI/ARDS. To investigate the role and underlying mechanisms of circulating monocytes and resident alveolar macrophages (AMs) in ALI/ARDS, we depleted circulating monocytes and AMs by clodronate-loaded liposome (CL) in lipopolysaccharide (LPS)-induced ALI/ARDS mouse model. Our results indicated that depletion of circulating monocytes by intravenous (i...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913425/cd36-mediates-h2o2-induced-calcium-influx-in-lung-microvascular-endothelial-cells
#3
Karthik Suresh, Laura Servinsky, Jose Reyes, Clark Undem, Joel Zaldumbide, Otgonchimeg Rentsendorj, Sruti Modekurty, Jeffrey M Dodd-O, Alan L Scott, David B Pearse, Larissa A Shimoda
Elevated levels of reactive oxygen species (ROS) and intracellular Ca2+ play a key role in endothelial barrier dysfunction in acute lung injury (ALI). We previously showed that H2O2-induced increases in intracellular calcium concentrations ([Ca2+]i) in LMVECs involve the membrane Ca2+ channel, transient receptor potential vanilloid-4 (TRPV4), and that inhibiting this channel attenuated H2O2-induced barrier disruption in vitro. We also showed that phosphorylation of TRPV4 by the Src family kinase, Fyn, contributes to H2O2-induced Ca2+ influx in LMVEC...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913424/digital-3d-reconstructions-using-histological-serial-sections-of-lung-tissue-including-the-alveolar-capillary-network
#4
Roman Grothausmann, Lars Knudsen, Matthias Ochs, Christian Mühlfeld
The alveolar capillary network (ACN) provides an enormously large surface area that is necessary for pulmonary gas exchange. Changes of the ACN during normal or pathological development or in pulmonary diseases are of great functional impact and warrant further analysis. Due to the complexity of the three-dimensional (3D) architecture of the ACN, 2D approaches are limited in providing a comprehensive impression of the characteristics of the normal ACN or the nature of its alterations. Stereological methods offer a quantitative way to assess the ACN in 3D in terms of capillary volume, surface area or number but lack a 3D visualization to interpret the data...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913423/bronchodilatory-effect-of-deep-inspiration-in-freshly-isolated-sheep-lungs
#5
William D Wong, Lu Wang, Peter D Paré, Chun Y Seow
Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913422/factor-xi-deficiency-enhances-the-pulmonary-allergic-response-to-house-dust-mite-in-mice-independent-of-factor-xii
#6
Ingrid Stroo, Jack Yang, Johannes Daan de Boer, Joris J T H Roelofs, Cornelis van 't Veer, Francis J Castellino, Sacha Zeerleder, Tom van der Poll
Asthma is associated with activation of coagulation in the airways. The coagulation system can be initiated via the extrinsic tissue factor dependent pathway or via the intrinsic pathway, in which the central player factor XI (FXI) can be either activated via active factor XII (FXIIa) or via thrombin. We aimed to determine the role of the intrinsic coagulation system, and its possible route of activation, in allergic lung inflammation induced by the clinically relevant human allergen house dust mite (HDM). Wild-type (WT), FXI knockout (KO) and FXII KO mice were subjected to repeated exposure to HDM via the airways, and inflammatory responses were compared...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913421/role-of-il-17a-in-murine-models-of-copd-airway-disease
#7
Haruhiko Yanagisawa, Mitsuo Hashimoto, Shunsuke Minagawa, Naoki Takasaka, Royce Ma, Catherine Moermans, Saburo Ito, Jun Araya, Alison Budelsky, Amanda Goodsell, Jody L Baron, Stephen L Nishimura
Small airway fibrosis is a major pathologic feature of chronic obstructive pulmonary disease (COPD) and is refractory to current treatments. Chronic inflammatory cells accumulate around small airways in COPD and are thought to play a major role in small airway fibrosis. Mice deficient in α/β T-cells have recently been shown to be protected from both experimental airway inflammation and fibrosis. In these models, CD4+Th17 cells and secretion of IL-17A are increased. However, a pathogenic role for IL-17 in specifically mediating fibrosis around airways has not been demonstrated...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27881407/prophylactic-and-therapeutic-treatment-with-flavonone-sakuranetin-ameliorates-lps-induced-acute-lung-injury
#8
Márcia Isabel Bittencourt-Mernak, Nathália Montouro Pinheiro, Fernanda P Roncon Santana, Marina P Guerreiro, Beatriz Mangueira Saraiva-Romanholo, Simone S Grecco, Luciana C Caperuto, Raphael J F Felizardo, Niels Olsen Saraiva Câmara, Iolanda F L Calvo Tibério, Mílton A Martins, João Henrique G Lago, Carla Máximo Prado
BACKGROUND AND PURPOSE: Sakuranetin is the main isolate flavonoid from Baccharis retusa (Asteraceae) leaves and exhibits anti-inflammatory and anti-oxidative activities. Acute respiratory distress syndrome is an acute failure of the respiratory system for which effective treatment is urgently necessary. This study investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. EXPERIMENTAL APPROACH: Animals were treated with intranasal sakuranetin 30 minutes before or 6 hours after instillation of LPS...
November 23, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27881406/enrichment-of-selective-mirnas-in-exosomes-and-delivery-of-exosomal-mirnas-in-vitro-and-in-vivo
#9
Duo Zhang, Heedoo Lee, Ziwen Zhu, Jasleen K Minhas, Yang Jin
Exosomes are nano vesicles secreted by cells, and contain various molecules including protein, lipid and DNA/RNA. They are crucial mediators of the intercellular communication and serve as promising vehicles for drug delivery and gene therapy. Recently, accumulating evidence suggest that microRNAs (miRNAs) may serve as new and potentially powerful targets for therapeutic interventions against various human diseases. However, steadily and effectively delivering miRNA mimics or inhibitors to target cells remains a major obstacle...
November 23, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27881405/effectiveness-of-individualised-lung-recruitment-strategies-at-birth-an-experimental-study-in-preterm-lambs
#10
David G Tingay, Anushi E Rajapaksa, Emanuela Zannin, Prue M Pereira-Fantini, Raffaele Dellacà, Elizabeth Perkins, Cornelis Elroy E Zonneveld, Andy Adler, Don Black, Inez Frerichs, Anna Lavizzari, Magdy Sourial, Bartłomiej Grychtol, Fabio Mosca, Peter G Davis
Respiratory transition at birth involves rapidly clearing fetal lung liquid and preventing efflux back into the lung whilst aeration is established. We have developed a sustained inflation (SIOPT) individualized to volume-response and a dynamic tidal positive end-expiratory pressure (open lung volume, OLV) strategy that both enhance this process. We aimed to compare the effect of each with a group managed with PEEP of 8 cmH2O and no recruitment manoeuvre (No-RM), on gas exchange, lung mechanics, spatiotemporal aeration and lung injury in 127±1d preterm lambs...
November 23, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27864288/the-role-of-nuclear-factor-erythroid-2-related-factor-2-nrf-2-in-the-protection-against-lung-injury
#11
Hailin Zhao, Shiori Eguchi, Azeem Alam, Daqing Ma
Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. Activation of Nrf2 has been shown to be protective against lung injury. In the lung, diverse stimuli including environmental oxidants, medicinal agents and pathogens can activate Nrf2. Nrf2 translocates to the nucleus and binds to an antioxidant response element (ARE). Through transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary injury, abnormal inflammatory and immune responses, and apoptosis...
November 18, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27864287/double-hit-mouse-model-of-cigarette-smoke-priming-for-acute-lung-injury
#12
Pavlo Sakhatskyy, Zhengke Wang, Diana Borgas, Joanne Lomas-Neira, Yaping Chen, Alfred Ayala, Sharon Rounds, Qing Lu
Epidemiologic studies indicate that cigarette smoking (CS) increases the risk and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The mechanism is not understood at least in part due to lack of animal models that reproduce the key features of CS priming process. In this study, using two strains of mice we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were pre-exposed to CS briefly (3 hours) or sub-acutely (3 weeks) before intra-tracheal instillation of LPS and ALI was assessed 18 hours after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation and alveolar apoptosis...
November 18, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27864286/transforming-growth-factor-%C3%AE-plays-divergent-roles-in-modulating-vascular-remodeling-inflammation-and-pulmonary-fibrosis-in-a-murine-model-of-scleroderma
#13
Kazuyuki Tsujino, Nilgun Isik Reed, Amha Atakilit, Xin Ren, Dean Sheppard
The efficacy and feasibility of targeting TGF-β in pulmonary fibrosis and lung vascular remodeling in systemic sclerosis (SSc) have not been well elucidated. In this study, we analyzed how blocking TGF-β signaling affects pulmonary abnormalities in fos-related antigen 2 (Fra-2) transgenic mice, a murine model that manifests three important lung pathological features of SSc: fibrosis, inflammation, and vascular remodeling. To interrupt TGF-β signaling in the Fra-2 transgenic mice, we used a pan-TGF-β blocking antibody, 1D11, and transgenic mice in which TGF-β receptor type 2 (Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (α-SMA-CreER; Tgfbr2flox/flox)...
November 18, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27864285/il-23-secreted-by-bronchial-epithelial-cells-contributes-allergic-sensitization-in-asthma-model
#14
Hyun Seung Lee, Da-Eun Park, Ji-Won Lee, Yuna Chang, Hye Young Kim, Woo-Jung Song, Hye-Ryun Kang, Heung-Woo Park, Yoon-Seok Chang, Sang-Heon Cho
BACKGROUND: IL-23 has been postulated to be a critical mediator contributing to various inflammatory diseases. Dermatophagoides pteronyssinus (Der p) is one of the most common inhalant allergens. However, the role of IL-23 in Der p-induced mouse asthma model is not well understood, particularly with regard to the development of allergic sensitization in the airways. OBJECTIVE: To evaluate roles of IL-23 in Der p-sensitization and asthma development. METHODS: BALB/c mice were repeatedly administered with Der p intra-nasally to develop Der p-allergic sensitization and asthma...
November 18, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27864284/region-specific-role-for-pten-in-maintenance-of-epithelial-phenotype-and-integrity
#15
Per Flodby, Janice Marie Liebler, Mitsuhiro Sunohara, Dan Ran, Alicia M McConnell, Manda Sai Krishnaveni, Agnes Banfalvi, Min Li, Barry R Stripp, Beiyun Zhou, Edward D Crandall, Parviz Minoo, Zea Borok
Previous studies have demonstrated resistance to naphthalene-induced injury in proximal airways of mice with lung epithelial-specific deletion of the tumor-suppressor gene Pten, attributed to increased proliferation of airway progenitors. We tested effects of Pten loss following bleomycin injury, a model typically used to study distal lung epithelial injury, in conditional PtenSFTPC-cre knockout mice. Pten-deficient airway epithelium exhibited marked hyperplasia, particularly in small bronchioles and at bronchoalveolar duct junctions, with reduced E-cadherin and β-catenin expression between cells towards the luminal aspect of the hyperplastic epithelium...
November 18, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27836902/active-versus-sedentary-lifestyle-from-weaning-to-adulthood-and-susceptibility-to-ozone-in-rats
#16
Christopher J Gordon, Pamela M Phillips, Allan Ledbetter, Samantha J Snow, M C Schladweiler, Andrew F M Johnstone, Urmilla P Kodavanti
The prevalence of a sedentary (SED) life style combined with calorically rich diets has spurred the rise in childhood obesity which, in turn, translates to adverse health effects in adulthood. Obesity and lack of active (ACT) lifestyle may increase susceptibility to air pollutants. We housed 22 day-old female Long-Evans rats in a cage without (SED) or with a running wheel (ACT). After 10 weeks the rats ran 310 ± 16.3 km (SEM). Responses of SED and ACT rats to whole-body O3 (0, 0.25, 0.5, or 1.0 ppm; 5 hr/day for 2 days) was assessed...
November 11, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27836901/deformation-induced-transitional-myofibroblasts-remodel-the-lung-during-compensatory-growth
#17
Robert D Bennett, Alexandra B Ysasi, Willi L Wagner, Cristian D Valenzuela, Akira Tsuda, Saumyadipta Pyne, Shuqiang Li, Jonna Grimsby, Prapti Pokharel, Kenneth J Livak, Maximilian Ackermann, Paul Blainey, Steven J Mentzer
In many mammals, including humans, removal of one lung (pneumonectomy) results in the compensatory growth of the remaining lung. Compensatory growth involves not only an increase in lung size, but also an increase in the number of alveoli in the peripheral lung; however, the process of compensatory neoalveolarization remains poorly understood. Here, we show that the expression of α-smooth muscle actin (SMA)-a cytoplasmic protein characteristic of myofibroblasts-is induced in the pleura following pneumonectomy...
November 11, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27836900/lethal-h1n1-influenza-a-virus-infection-alters-the-murine-alveolar-type-ii-cell-surfactant-lipidome
#18
Parker S Woods, Lauren May Doolittle, Lucia Elena Rosas, Lisa M Joseph, Edward P Calomeni, Ian Christopher Davis
BACKGROUND: Alveolar type II (ATII) epithelial cells are the primary site of influenza virus replication in the distal lung. Development of acute respiratory distress syndrome (ARDS) in influenza-infected mice correlates with significant alterations in ATII cell function. However, the impact of infection on ATII cell surfactant lipid metabolism has never been explored. METHODS: C57BL/6 mice were inoculated intranasally with 10,000 pfu/mouse of influenza A/WSN/33 (H1N1) or mock-infected with virus diluent...
November 11, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27836899/trail-signaling-is-pro-inflammatory-and-pro-viral-in-a-murine-model-of-rhinovirus-1b-infection
#19
Jason L Girkin, Luke Hatchwell, Adam M Collison, Malcolm R Starkey, Philip M Hansbro, Hideo Yagita, Paul S Foster, Joerg Mattes
The aim of this study is to elucidate the role of TRAIL during rhinovirus (RV) infection in vivo. Naïve wild type and TRAIL-deficient (Tnfsf10-/-) BALB/c mice were infected intranasally with RV1B. In separate experiments, Tnfsf10-/- mice were sensitized and challenged via the airway route with house dust mite (HDM) to induce allergic airways disease and then challenged with RVIB or UV-RVIB. Airways hyperreactivity (AHR) was invasively assessed as total airways resistance in response to increasing methacholine challenge and inflammation assessed in bronchoalveolar lavage fluid (BALF) at multiple time points post infection...
November 11, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27836898/dung-biomass-smoke-activates-inflammatory-signaling-pathways-in-human-small-airway-epithelial-cells
#20
Claire E McCarthy, Parker F Duffney, Robert Gelein, Thomas H Thatcher, Alison C P Elder, Richard P Phipps, Patricia J Sime
Animal dung is a biomass fuel burned by vulnerable populations who cannot afford cleaner sources of energy, such as wood and gas, for cooking and heating their homes. Exposure to biomass smoke is the leading environmental risk for mortality, with over 4 million deaths each year worldwide attributed to indoor air pollution from biomass smoke. Biomass smoke inhalation is epidemiologically associated with pulmonary diseases, including Chronic Obstructive Pulmonary Disease (COPD), lung cancer, and respiratory infections, especially in low and middle-income countries...
November 11, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
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