AJP: Lung Cellular and Molecular Physiology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Acid sphingomyelinase mediates murine acute lung injury following transfusion of aged platelets
Pulmonary complications from stored blood products are the leading cause of mortality related to transfusion. Transfusion-related acute lung injury is mediated by antibodies or bioactive mediators, yet underlying mechanisms are incompletely understood. Sphingolipids such as ceramide regulate lung injury, and their composition changes as a function of time in stored blood. Here, we tested the hypothesis that aged platelets may induce lung injury via a sphingolipid-mediated mechanism. To assess this hypothesis, a two-hit mouse model was devised. Recipient mice were treated with 2 mg/kg intraperitoneal lipopolysaccharide (pri...
Source: AJP: Lung Cellular and Molecular Physiology - May 1, 2017 Category: Respiratory Medicine Authors: McVey, M. J., Kim, M., Tabuchi, A., Srbely, V., Japtok, L., Arenz, C., Rotstein, O., Kleuser, B., Semple, J. W., Kuebler, W. M. Tags: RESEARCH ARTICLE Source Type: research

Central role of T helper 17 cells in chronic hypoxia-induced pulmonary hypertension
Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4+ T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4+ T cells, specifically the T helper 17 subset, contribute to chronic hyp...
Source: AJP: Lung Cellular and Molecular Physiology - May 1, 2017 Category: Respiratory Medicine Authors: Maston, L. D., Jones, D. T., Giermakowska, W., Howard, T. A., Cannon, J. L., Wang, W., Wei, Y., Xuan, W., Resta, T. C., Gonzalez Bosc, L. V. Tags: RESEARCH ARTICLE Source Type: research

Hypoxia inhibits expression and function of mitochondrial thioredoxin 2 to promote pulmonary hypertension
In conclusion, Trx2 overexpression failed to attenuate hypoxia-induced HPASMC proliferation in vitro or hypoxia-induced PH in vivo. These findings indicate that strategies to enhance Trx2 expression are unlikely to exert therapeutic effects in PH pathogenesis. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - May 1, 2017 Category: Respiratory Medicine Authors: Adesina, S. E., Wade, B. E., Bijli, K. M., Kang, B.-Y., Williams, C. R., Ma, J., Go, Y.-M., Hart, C. M., Sutliff, R. L. Tags: RESEARCH ARTICLE Source Type: research

Attenuation of endoplasmic reticulum stress by caffeine ameliorates hyperoxia-induced lung injury
In conclusion, hyperoxia-induced alveolar growth impairment is mediated, in part, by ER stress. Early caffeine treatment protects developing lungs from hyperoxia-induced injury by attenuating ER stress. (Source: AJP: Lung Cellular and Molecular Physiology)
Source: AJP: Lung Cellular and Molecular Physiology - May 1, 2017 Category: Respiratory Medicine Authors: Teng, R.-J., Jing, X., Michalkiewicz, T., Afolayan, A. J., Wu, T.-J., Konduri, G. G. Tags: RESEARCH ARTICLE Source Type: research

Higher mini-BAL total protein concentration in early ARDS predicts faster resolution of lung injury measured by more ventilator-free days
The protein concentration of alveolar edema fluid in acute respiratory distress syndrome (ARDS) is dynamic. It reflects alveolar flooding during acute injury, as well as fluid and protein clearance over time. We hypothesized that among ARDS patients treated with low tidal volume ventilation, higher concentrations of protein in mini-bronchoalveolar lavage (mBAL) samples would predict slower resolution of lung injury and worse clinical outcomes. Total protein and IgM concentrations in day 0 mBAL samples from 79 subjects enrolled in the aerosolized albuterol (ALTA) ARDS Network Albuterol Trial were measured by colorimetric as...
Source: AJP: Lung Cellular and Molecular Physiology - May 1, 2017 Category: Respiratory Medicine Authors: Hendrickson, C. M., Abbott, J., Zhuo, H., Liu, K. D., Calfee, C. S., Matthay, M. A., NHLBI ARDS Network Tags: RESEARCH ARTICLE Source Type: research

Hypoxia induces arginase II expression and increases viable human pulmonary artery smooth muscle cell numbers via AMPK{alpha}1 signaling
Pulmonary artery smooth muscle cell (PASMC) proliferation is one of the hallmark features of hypoxia-induced pulmonary hypertension. With only supportive treatment options available for this life-threatening disease, treating and preventing the proliferation of PASMCs is a viable therapeutic option. A key promoter of hypoxia-induced increases in the number of viable human PASMCs is arginase II, with attenuation of viable cell numbers following pharmacologic inhibition or siRNA knockdown of the enzyme. Additionally, increased levels of arginase have been demonstrated in the pulmonary vasculature of patients with pulmonary h...
Source: AJP: Lung Cellular and Molecular Physiology - April 5, 2017 Category: Respiratory Medicine Authors: Xue, J., Nelin, L. D., Chen, B. Tags: RESEARCH ARTICLE Source Type: research

Lung pericyte-like cells are functional interstitial immune sentinel cells
Pericytes are perivascular PDGF receptor-β+ (PDGFRβ+) stromal cells required for vasculogenesis and maintenance of microvascular homeostasis in many organs. Because of their unique juxtaposition to microvascular endothelium, lung PDGFRβ+ cells are well situated to detect proinflammatory molecules released following epithelial injury and promote acute inflammatory responses. Thus we hypothesized that these cells represent an unrecognized immune surveillance or injury-sentinel interstitial cell. To evaluate this hypothesis, we isolated PDGFRβ+ cells from murine lung and demonstrated that they have charact...
Source: AJP: Lung Cellular and Molecular Physiology - April 5, 2017 Category: Respiratory Medicine Authors: Hung, C. F., Mittelsteadt, K. L., Brauer, R., McKinney, B. L., Hallstrand, T. S., Parks, W. C., Chen, P., Schnapp, L. M., Liles, W. C., Duffield, J. S., Altemeier, W. A. Tags: RESEARCH ARTICLE Source Type: research

Prenatal exposure to tobacco smoke sex dependently influences methylation and mRNA levels of the Igf axis in lungs of mouse offspring
Prenatal smoke exposure is a risk factor for abnormal lung development and increased sex-dependent susceptibility for asthma and chronic obstructive pulmonary disease (COPD). Birth cohort studies show genome-wide DNA methylation changes in children from smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. The insulin-like growth factor (IGF) system plays an important role in lung development. We hypothesized that prenatal exposure to smoke induces lasting changes in promoter methylation patterns of Igf1 and Igf1r, thus influencing transcriptional activity and contributing to abnormal lung devel...
Source: AJP: Lung Cellular and Molecular Physiology - April 5, 2017 Category: Respiratory Medicine Authors: Meyer, K. F., Krauss-Etschmann, S., Kooistra, W., Reinders-Luinge, M., Timens, W., Kobzik, L., Plösch, T., Hylkema, M. N. Tags: RESEARCH ARTICLE Source Type: research

Protein biomarkers associated with primary graft dysfunction following lung transplantation
Severe primary graft dysfunction affects 15–20% of lung transplant recipients and carries a high mortality risk. In addition to known donor, recipient, and perioperative clinical risk factors, numerous biologic factors are thought to contribute to primary graft dysfunction. Our current understanding of the pathogenesis of lung injury and primary graft dysfunction emphasizes multiple pathways leading to lung endothelial and epithelial injury. Protein biomarkers specific to these pathways can be measured in the plasma, bronchoalveolar lavage fluid, and lung tissue. Clarification of the pathophysiology and timing of pri...
Source: AJP: Lung Cellular and Molecular Physiology - April 5, 2017 Category: Respiratory Medicine Authors: Hamilton, B. C. S., Kukreja, J., Ware, L. B., Matthay, M. A. Tags: REVIEW Source Type: research

Vagal innervation is required for pulmonary function phenotype in Htr4-/- mice
We report here that the Htr4–/– phenotype in mouse is dependent on vagal innervation to the lung. Both ex vivo tracheal ring reactivity and in vivo flexiVent pulmonary functional analyses demonstrate that vagotomy abrogates the Htr4–/– airway hyperresponsiveness phenotype. Hyperpolarized 3He gas magnetic resonance imaging and stereological assessment of wild-type and Htr4–/– mice reveal no observable differences in lung volume, inflation characteristics, or pulmonary microarchitecture. Finally, control of breathing experiments reveal substantive differences in baseline breathing characte...
Source: AJP: Lung Cellular and Molecular Physiology - April 1, 2017 Category: Respiratory Medicine Authors: House, J. S., Nichols, C. E., Li, H., Brandenberger, C., Virgincar, R. S., DeGraff, L. M., Driehuys, B., Zeldin, D. C., London, S. J. Tags: RESEARCH ARTICLE Source Type: research

Ca2+/calmodulin-dependent protein kinase II{beta} and II{delta} mediate TGF{beta}-induced transduction of fibronectin and collagen in human pulmonary fibroblasts
In this study, we examined the interactions between calcium signaling, activation of CamK and other kinases, and extracellular matrix (ECM) gene expression. Human pulmonary fibroblasts were cultured and stimulated with artificially generated Ca2+ pulses in the absence of TGFβ, or with TGFβ (1 nM) or vehicle in the presence of various blockers of Ca2+ signaling. PCR and Western blotting were used to measure gene expression and protein levels, respectively. We found that Ca2+ pulses in the absence of TGFβ increased ECM gene expression in a pulse frequency-dependent manner, and that blocking Ca2+ signaling and ...
Source: AJP: Lung Cellular and Molecular Physiology - April 1, 2017 Category: Respiratory Medicine Authors: Mukherjee, S., Sheng, W., Sun, R., Janssen, L. J. Tags: RESEARCH ARTICLE Source Type: research

HIV infection model of chronic obstructive pulmonary disease in mice
Cigarette smoke usage is prevalent in human immunodeficiency virus (HIV)-positive patients, and, despite highly active antiretroviral therapy, these individuals develop an accelerated form of chronic obstructive pulmonary disease (COPD). Studies investigating the mechanisms of COPD development in HIV have been limited by the lack of suitable mouse models. Here we describe a model of HIV-induced COPD in wild-type mice using EcoHIV, a chimeric HIV capable of establishing chronic infection in immunocompetent mice. A/J mice were infected with EcoHIV and subjected to whole body cigarette smoke exposure. EcoHIV was detected in a...
Source: AJP: Lung Cellular and Molecular Physiology - April 1, 2017 Category: Respiratory Medicine Authors: Geraghty, P., Hadas, E., Kim, B.-H., Dabo, A. J., Volsky, D. J., Foronjy, R. Tags: RESEARCH ARTICLE Source Type: research

Magnetic resonance imaging of disease progression and resolution in a transgenic mouse model of pulmonary fibrosis
We examined the ability of magnetic resonance imaging (MRI) to noninvasively assess lung fibrosis progression and resolution in a doxycycline (Dox) regulatable, transgenic mouse model that overexpresses transforming growth factor-α (TGF-α) under control of a lung-epithelial-specific promoter. During 7 wk of Dox treatment, fibrotic lesions were readily observed as high-signal tissue. Mean weighted signal and percent signal volume were found to be the most robust MRI-derived measures of fibrosis, and these metrics correlated significantly with pleural thickness, histology scores, and hydroxyproline content (R = 0...
Source: AJP: Lung Cellular and Molecular Physiology - April 1, 2017 Category: Respiratory Medicine Authors: Cleveland, Z. I., Zhou, Y. M., Akinyi, T. G., Dunn, R. S., Davidson, C. R., Guo, J., Woods, J. C., Hardie, W. D. Tags: RESEARCH ARTICLE Source Type: research

Hydrogen peroxide is a critical regulator of the hypoxia-induced alterations of store-operated Ca2+ entry into rat pulmonary arterial smooth muscle cells
To investigate the association between store-operated Ca2+ entry (SOCE) and reactive oxygen species (ROS) during hypoxia, this study determined the changes of transient receptor potential canonical 1 (TRPC1) and Orai1, two candidate proteins for store-operated Ca2+ (SOC) channels and their gate regulator, stromal interaction molecule 1 (STIM1), in a hypoxic environment and their relationship with ROS in pulmonary arterial smooth muscle cells (PASMCs). Exposure to hypoxia caused a transient Ca2+ spike and subsequent Ca2+ plateau of SOCE to be intensified in PASMCs when TRPC1, STIM1, and Orai1 were upregulated. SOCE in cells...
Source: AJP: Lung Cellular and Molecular Physiology - April 1, 2017 Category: Respiratory Medicine Authors: Chen, T.-X., Xu, X.-Y., Zhao, Z., Zhao, F.-Y., Gao, Y.-M., Yan, X.-H., Wan, Y. Tags: RESEARCH ARTICLE Source Type: research

Endothelial cell signaling and ventilator-induced lung injury: molecular mechanisms, genomic analyses, and therapeutic targets
Mechanical ventilation is a life-saving intervention in critically ill patients with respiratory failure due to acute respiratory distress syndrome (ARDS). Paradoxically, mechanical ventilation also creates excessive mechanical stress that directly augments lung injury, a syndrome known as ventilator-induced lung injury (VILI). The pathobiology of VILI and ARDS shares many inflammatory features including increases in lung vascular permeability due to loss of endothelial cell barrier integrity resulting in alveolar flooding. While there have been advances in the understanding of certain elements of VILI and ARDS pathobiolog...
Source: AJP: Lung Cellular and Molecular Physiology - April 1, 2017 Category: Respiratory Medicine Authors: Wang, T., Gross, C., Desai, A. A., Zemskov, E., Wu, X., Garcia, A. N., Jacobson, J. R., Yuan, J. X.- J., Garcia, J. G. N., Black, S. M. Tags: REVIEW Source Type: research