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Author Birgitt Gutbier

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Neutralizing Complement C5a Protects Mice with Pneumococcal Pulmonary Sepsis.

Holger Müller-Redetzky, Ute Kellermann, Sandra-Maria Wienhold, Birgitt Gutbier, Jasmin Lienau, Katharina Hellwig, Katrin Reppe, Eleftheria Letsiou, Thomas Tschernig, Markus Scholz, Peter Ahnert, Christian Maasch, Kai Hoehlig, Sven Klussmann, Axel Vater, Theresa C Firsching, Judith Hoppe, Norbert Suttorp, Martin Witzenrath,

BACKGROUND:Community-acquired pneumonia and associated sepsis cause high mortality despite antibiotic treatment. Uncontrolled inflammatory host responses contribute to the unfavorable outcome by driving lung and extrapulmonary organ failure. The complement fragment C5a holds significant proinflammatory functions and is associated with tissue damage in various inflammatory conditions. The authors hypothesized that C5a ... Read more >>

Anesthesiology (Anesthesiology)
[2020, 132(4):795-807]

Cited: 0 times

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Acute Moraxella catarrhalis Airway Infection of Chronically Smoke-Exposed Mice Increases Mechanisms of Emphysema Development: A Pilot Study.

Katja Fischer, Jan-Moritz Doehn, Christian Herr, Carolin Lachner, Annina Heinrich, Olivia Kershaw, Meike Voss, Max H Jacobson, Achim D Gruber, Matthias Clauss, Martin Witzenrath, Robert Bals, Birgitt Gutbier, Hortense Slevogt,

In chronic obstructive pulmonary disease (COPD), acute exacerbations and emphysema development are characteristics for disease pathology. COPD is complicated by infectious exacerbations with acute worsening of respiratory symptoms with Moraxella catarrhalis as one of the most frequent pathogens. Although cigarette smoke (CS) is the primary risk factor, additional molecular mechanisms ... Read more >>

Eur J Microbiol Immunol (Bp) (European journal of microbiology & immunology)
[2018, 8(4):128-134]

Cited: 0 times

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Prognostic and Pathogenic Role of Angiopoietin-1 and -2 in Pneumonia.

Birgitt Gutbier, Anne-Kathrin Neuhauß, Katrin Reppe, Carolin Ehrler, Ansgar Santel, Jörg Kaufmann, Markus Scholz, Norbert Weissmann, Lars Morawietz, Timothy J Mitchell, Stefano Aliberti, Stefan Hippenstiel, Norbert Suttorp, Martin Witzenrath, ,

RATIONALE:During pneumonia, pathogen-host interaction evokes inflammation and lung barrier dysfunction. Tie2 activation by angiopoietin-1 reduces, whereas Tie2 blockade by angiopoietin-2 increases, inflammation and permeability during sepsis. The role of angiopoietin-1/-2 in pneumonia remains unidentified. OBJECTIVES:To investigate the prognostic and pathogenic impact of angiopoietins in regulating pulmonary vascular barrier function and ... Read more >>

Am. J. Respir. Crit. Care Med. (American journal of respiratory and critical care medicine)
[2018, 198(2):220-231]

Cited: 6 times

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Antibiotic treatment-induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia.

Oliver H Robak, Markus M Heimesaat, Andrey A Kruglov, Sandra Prepens, Justus Ninnemann, Birgitt Gutbier, Katrin Reppe, Hubertus Hochrein, Mark Suter, Carsten J Kirschning, Veena Marathe, Jan Buer, Mathias W Hornef, Markus Schnare, Pascal Schneider, Martin Witzenrath, Stefan Bereswill, Ulrich Steinhoff, Norbert Suttorp, Leif E Sander, Catherine Chaput, Bastian Opitz,

Broad-spectrum antibiotics are widely used with patients in intensive care units (ICUs), many of whom develop hospital-acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa-induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2018, 128(8):3535-3545]

Cited: 10 times

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Digital Image Analyses on Whole-Lung Slides in Mouse Models of Acute Pneumonia.

Kristina Dietert, Geraldine Nouailles, Birgitt Gutbier, Katrin Reppe, Sarah Berger, Xiaohui Jiang, Anja E Schauer, Andreas C Hocke, Susanne Herold, Hortense Slevogt, Martin Witzenrath, Norbert Suttorp, Achim D Gruber,

Descriptive histopathology of mouse models of pneumonia is essential in assessing the outcome of infections, molecular manipulations, or therapies in the context of whole lungs. Quantitative comparisons between experimental groups, however, have been limited to laborious stereology or ill-defined scoring systems that depend on the subjectivity of a more or ... Read more >>

Am. J. Respir. Cell Mol. Biol. (American journal of respiratory cell and molecular biology)
[2018, 58(4):440-448]

Cited: 1 time

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Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia.

Kristina Dietert, Birgitt Gutbier, Sandra M Wienhold, Katrin Reppe, Xiaohui Jiang, Ling Yao, Catherine Chaput, Jan Naujoks, Markus Brack, Alexandra Kupke, Christin Peteranderl, Stephan Becker, Carolin von Lachner, Nelli Baal, Hortense Slevogt, Andreas C Hocke, Martin Witzenrath, Bastian Opitz, Susanne Herold, Holger Hackstein, Leif E Sander, Norbert Suttorp, Achim D Gruber,

Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress ... Read more >>

PLoS ONE (PloS one)
[2017, 12(11):e0188251]

Cited: 5 times

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Sphingosine Kinase 1 Regulates Inflammation and Contributes to Acute Lung Injury in Pneumococcal Pneumonia via the Sphingosine-1-Phosphate Receptor 2.

Birgitt Gutbier, Stefanie M Schönrock, Carolin Ehrler, Rainer Haberberger, Kristina Dietert, Achim D Gruber, Wolfgang Kummer, Laura Michalick, Wolfgang M Kuebler, Andreas C Hocke, Kolja Szymanski, Eleftheria Letsiou, Anja Lüth, Fabian Schumacher, Burkhard Kleuser, Timothy J Mitchell, Wilhelm Bertrams, Bernd Schmeck, Denise Treue, Frederick Klauschen, Torsten T Bauer, Mario Tönnies, Norbert Weissmann, Stefan Hippenstiel, Norbert Suttorp, Martin Witzenrath, ,

OBJECTIVES:Severe pneumonia may evoke acute lung injury, and sphingosine-1-phosphate is involved in the regulation of vascular permeability and immune responses. However, the role of sphingosine-1-phosphate and the sphingosine-1-phosphate producing sphingosine kinase 1 in pneumonia remains elusive. We examined the role of the sphingosine-1-phosphate system in regulating pulmonary vascular barrier function ... Read more >>

Crit. Care Med. (Critical care medicine)
[2018, 46(3):e258-e267]

Cited: 2 times

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Vasculotide reduces pulmonary hyperpermeability in experimental pneumococcal pneumonia.

Birgitt Gutbier, Xiaohui Jiang, Kristina Dietert, Carolin Ehrler, Jasmin Lienau, Paul Van Slyke, Harold Kim, Van C Hoang, Jason T Maynes, Daniel J Dumont, Achim D Gruber, Norbert Weissmann, Timothy J Mitchell, Norbert Suttorp, Martin Witzenrath,

<label>BACKGROUND</label>Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality worldwide. Despite effective antimicrobial therapy, CAP can induce pulmonary endothelial hyperpermeability resulting in life-threatening lung failure due to an exaggerated host-pathogen interaction. Treatment of acute lung injury is mainly supportive because key elements of inflammation-induced barrier disruption remain undetermined. ... Read more >>

Crit Care (Critical care (London, England))
[2017, 21(1):274]

Cited: 5 times

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Moraxella catarrhalis induces an immune response in the murine lung that is independent of human CEACAM5 expression and long-term smoke exposure.

Birgitt Gutbier, Katja Fischer, Jan-Moritz Doehn, Carolin von Lachner, Christian Herr, Esther Klaile, Ursula Frischmann, Bernhard B Singer, Kristian Riesbeck, Wolfgang Zimmermann, Norbert Suttorp, Sebastian Bachmann, Robert Bals, Martin Witzenrath, Hortense Slevogt,

In patients with chronic obstructive pulmonary disease (COPD), Moraxella catarrhalis infection of the lower airways is associated with chronic colonization and inflammation during stable disease and acute exacerbations. Chronic smoke exposure induces chronic inflammation and impairs mucociliary clearance, thus contributing to bacterial colonization of the lower airways in COPD patients. ... Read more >>

Am. J. Physiol. Lung Cell Mol. Physiol. (American journal of physiology. Lung cellular and molecular physiology)
[2015, 309(3):L250-61]

Cited: 7 times

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CFTR and sphingolipids mediate hypoxic pulmonary vasoconstriction.

Christoph Tabeling, Hanpo Yu, Liming Wang, Hannes Ranke, Neil M Goldenberg, Diana Zabini, Elena Noe, Adrienn Krauszman, Birgitt Gutbier, Jun Yin, Michael Schaefer, Christoph Arenz, Andreas C Hocke, Norbert Suttorp, Richard L Proia, Martin Witzenrath, Wolfgang M Kuebler,

Hypoxic pulmonary vasoconstriction (HPV) optimizes pulmonary ventilation-perfusion matching in regional hypoxia, but promotes pulmonary hypertension in global hypoxia. Ventilation-perfusion mismatch is a major cause of hypoxemia in cystic fibrosis. We hypothesized that cystic fibrosis transmembrane conductance regulator (CFTR) may be critical in HPV, potentially by modulating the response to sphingolipids ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2015, 112(13):E1614-23]

Cited: 26 times

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Surfactant protein A mediates pulmonary clearance of Staphylococcus aureus.

Nils T Veith, Thomas Tschernig, Birgitt Gutbier, Martin Witzenrath, Carola Meier, Michael Menger, Markus Bischoff,

Surfactant protein A has been shown to enhance opsonization and clearance of Staphylococcus aureus in vitro. Here, the phagocytosis of alveolar S. aureus was investigated in vivo using intravital microscopy. Fluorescence labelled S. aureus Newman cells were intratracheally administered to anesthetized mice and the alveolar surface was observed for fifteen ... Read more >>

Respir. Res. (Respiratory research)
[2014, 15:85]

Cited: 8 times

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Nucleotide oligomerization domain 1 ligation suppressed murine allergen-specific T-cell proliferation and airway hyperresponsiveness.

Christoph Tabeling, Heide Scheer, Stefanie M Schönrock, Franziska Runge, Birgitt Gutbier, Jasmin Lienau, Eckard Hamelmann, Bastian Opitz, Norbert Suttorp, Konstantin Mayer, Georg M Behrens, Thomas Tschernig, Martin Witzenrath,

The cytosolic nucleotide oligomerization domain (NOD)-like receptors NOD1 and NOD2 are important contributors to the intracellular recognition of pathogens including Chlamydophila pneumoniae, but little is known about their influence on allergen-induced airway inflammation. In BALB/c mice, we observed that infection with C. pneumoniae before systemic sensitization with ovalbumin (OVA) and ... Read more >>

Am. J. Respir. Cell Mol. Biol. (American journal of respiratory cell and molecular biology)
[2014, 50(5):903-911]

Cited: 5 times

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Delivery of the endolysin Cpl-1 by inhalation rescues mice with fatal pneumococcal pneumonia.

Jan M Doehn, Katja Fischer, Katrin Reppe, Birgitt Gutbier, Thomas Tschernig, Andreas C Hocke, Vincent A Fischetti, Jutta Löffler, Norbert Suttorp, Stefan Hippenstiel, Martin Witzenrath,

OBJECTIVES: Pneumonia is associated with a high morbidity and mortality worldwide. Streptococcus pneumoniae remains the most common cause of pneumonia, and pneumococcal antibiotic resistance is increasing. The purified bacteriophage endolysin Cpl-1 rapidly and specifically kills pneumococci. We tested the hypothesis that a single dose of recombinant aerosolized Cpl-1 would rescue ... Read more >>

J. Antimicrob. Chemother. (The Journal of antimicrobial chemotherapy)
[2013, 68(9):2111-2117]

Cited: 24 times

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Streptococcus pneumoniae stimulates a STING- and IFN regulatory factor 3-dependent type I IFN production in macrophages, which regulates RANTES production in macrophages, cocultured alveolar epithelial cells, and mouse lungs.

Uwe Koppe, Katrin Högner, Jan-Moritz Doehn, Holger C Müller, Martin Witzenrath, Birgitt Gutbier, Stefan Bauer, Thomas Pribyl, Sven Hammerschmidt, Jürgen Lohmeyer, Norbert Suttorp, Susanne Herold, Bastian Opitz,

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. In this study, we examine an innate immune recognition pathway that senses pneumococcal infection, triggers type I IFN production, and regulates RANTES production. We found that human and murine alveolar macrophages as well as murine bone marrow macrophages, but not alveolar ... Read more >>

J. Immunol. (Journal of immunology (Baltimore, Md. : 1950))
[2012, 188(2):811-817]

Cited: 50 times

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Streptococcus pneumoniae-induced regulation of cyclooxygenase-2 in human lung tissue.

Kolja V Szymanski, Mario Toennies, Anne Becher, Diana Fatykhova, Philippe D N'Guessan, Birgitt Gutbier, Frederick Klauschen, Frank Neuschaefer-Rube, Paul Schneider, Jens Rueckert, Jens Neudecker, Torsten T Bauer, Klaus Dalhoff, Daniel Drömann, Achim D Gruber, Olivia Kershaw, Bettina Temmesfeld-Wollbrueck, Norbert Suttorp, Stefan Hippenstiel, Andreas C Hocke,

The majority of cases of community-acquired pneumonia are caused by Streptococcus pneumoniae and most studies on pneumococcal host interaction are based on cell culture or animal experiments. Thus, little is known about infections in human lung tissue. Cyclooxygenase-2 and its metabolites play an important regulatory role in lung inflammation. Therefore, ... Read more >>

Eur. Respir. J. (The European respiratory journal)
[2012, 40(6):1458-1467]

Cited: 17 times

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The Sphingosine-1 Phosphate receptor agonist FTY720 dose dependently affected endothelial integrity in vitro and aggravated ventilator-induced lung injury in mice.

Holger Christian Müller, Andreas Christian Hocke, Katharina Hellwig, Birgitt Gutbier, Harm Peters, Stefanie Maria Schönrock, Thomas Tschernig, Andreas Schmiedl, Stefan Hippenstiel, Philippe Dje N'Guessan, Simone Rosseau, Norbert Suttorp, Martin Witzenrath,

Lung barrier protection by Sphingosine-1 Phosphate (S1P) has been demonstrated experimentally, but recent evidence suggests barrier disruptive properties of high systemic S1P concentrations. The S1P analog FTY720 recently gained an FDA approval for treatment of multiple sclerosis. In case of FTY720 treated patients experiencing multiple organ dysfunction syndrome the drug ... Read more >>

Pulm Pharmacol Ther (Pulmonary pharmacology & therapeutics)
[2011, 24(4):377-385]

Cited: 20 times

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The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia.

Martin Witzenrath, Florence Pache, Daniel Lorenz, Uwe Koppe, Birgitt Gutbier, Christoph Tabeling, Katrin Reppe, Karolin Meixenberger, Anca Dorhoi, Jiangtao Ma, Ashleigh Holmes, George Trendelenburg, Markus M Heimesaat, Stefan Bereswill, Mark van der Linden, Jürg Tschopp, Timothy J Mitchell, Norbert Suttorp, Bastian Opitz,

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and sepsis. Pneumococci can be divided into >90 serotypes that show differences in the pathogenicity and invasiveness. We tested the hypotheses that the innate immune inflammasome pathway is involved in fighting pneumococcal pneumonia and that some invasive pneumococcal types are not ... Read more >>

J. Immunol. (Journal of immunology (Baltimore, Md. : 1950))
[2011, 187(1):434-440]

Cited: 123 times

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Adrenomedullin attenuates ventilator-induced lung injury in mice.

Holger Christian Müller, Martin Witzenrath, Thomas Tschernig, Birgitt Gutbier, Stefan Hippenstiel, Ansgar Santel, Norbert Suttorp, Simone Rosseau,

BACKGROUND: Mechanical ventilation (MV) is a life-saving intervention in acute respiratory failure without any alternative. However, even protective ventilation strategies applying minimal mechanical stress may evoke ventilator-induced lung injury (VILI). Adjuvant pharmacological strategies in addition to lung-protective ventilation to attenuate VILI are lacking. Adrenomedullin exhibited endothelial barrier-stabilising properties in vitro ... Read more >>

Thorax (Thorax)
[2010, 65(12):1077-1084]

Cited: 24 times

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Simvastatin attenuates ventilator-induced lung injury in mice.

Holger C Müller, Katharina Hellwig, Simone Rosseau, Thomas Tschernig, Andreas Schmiedl, Birgitt Gutbier, Bernd Schmeck, Stefan Hippenstiel, Harm Peters, Lars Morawietz, Norbert Suttorp, Martin Witzenrath,

Mechanical ventilation (MV) is a life saving intervention in acute respiratory failure without alternative. However, particularly in pre-injured lungs, even protective ventilation strategies may evoke ventilator-induced lung injury (VILI), which is characterized by pulmonary inflammation and vascular leakage. Adjuvant pharmacologic strategies in addition to lung protective ventilation to attenuate VILI ... Read more >>

Crit Care (Critical care (London, England))
[2010, 14(4):R143]

Cited: 37 times

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RNAi-mediated suppression of constitutive pulmonary gene expression by small interfering RNA in mice.

Birgitt Gutbier, Stefanie M Kube, Katrin Reppe, Ansgar Santel, Christian Lange, Jörg Kaufmann, Norbert Suttorp, Martin Witzenrath,

The ability of synthetic small interfering RNA (siRNA) to silence gene expression makes it a useful tool in biomedical research. However, effective and non-toxic functional siRNA delivery to mouse lungs in vivo is still a key challenge, and regulation of constitutively expressed genes is poorly characterized. Following in vitro validation ... Read more >>

Pulm Pharmacol Ther (Pulmonary pharmacology & therapeutics)
[2010, 23(4):334-344]

Cited: 19 times

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Systemic use of the endolysin Cpl-1 rescues mice with fatal pneumococcal pneumonia.

Martin Witzenrath, Bernd Schmeck, Jan M Doehn, Thomas Tschernig, Janine Zahlten, Jutta M Loeffler, Maren Zemlin, Holger Müller, Birgitt Gutbier, Hartwig Schütte, Stefan Hippenstiel, Vincent A Fischetti, Norbert Suttorp, Simone Rosseau,

OBJECTIVES: Community-acquired pneumonia is a very common infectious disease associated with significant morbidity and mortality. Streptococcus pneumoniae is the predominant pathogen in this disease, and pneumococcal resistance to multiple antibiotics is increasing. The recently purified bacteriophage endolysin Cpl-1 rapidly and specifically kills pneumococci on contact. The aim of this study ... Read more >>

Crit. Care Med. (Critical care medicine)
[2009, 37(2):642-649]

Cited: 51 times

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Phosphodiesterase 2 inhibition diminished acute lung injury in murine pneumococcal pneumonia.

Martin Witzenrath, Birgitt Gutbier, Bernd Schmeck, Herrmann Tenor, Joachim Seybold, Raimund Kuelzer, Guido Grentzmann, Armin Hatzelmann, Vincent van Laak, Thomas Tschernig, Timothy J Mitchell, Christian Schudt, Simone Rosseau, Norbert Suttorp, Hartwig Schütte,

OBJECTIVE: Severe pneumococcal pneumonia frequently causes respiratory failure. Both pathogen factors and an uncontrolled host response may contribute to acute lung injury by impairing microvascular barrier function. Phosphodiesterase 2 (PDE2) was examined as a potential target in pneumonia-induced lung microvascular hyperpermeability. DESIGN: Controlled, in vitro, ex vivo, and in vivo ... Read more >>

Crit. Care Med. (Critical care medicine)
[2009, 37(2):584-590]

Cited: 12 times

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Immunostimulation with macrophage-activating lipopeptide-2 increased survival in murine pneumonia.

Katrin Reppe, Thomas Tschernig, Anke Lührmann, Vincent van Laak, Karsten Grote, Maren V Zemlin, Birgitt Gutbier, Holger C Müller, Mischo Kursar, Hartwig Schütte, Simone Rosseau, Reinhard Pabst, Norbert Suttorp, Martin Witzenrath,

Community-acquired pneumonia (CAP) is associated with high morbidity and mortality, and Streptococcus pneumoniae is the most prevalent causal pathogen identified in CAP. Impaired pulmonary host defense increases susceptibility to pneumococcal pneumonia. S. pneumoniae may up-regulate Toll-like receptor (TLR)-2 expression and activate TLR-2, contributing to pneumococcus-induced immune responses. In the current ... Read more >>

Am. J. Respir. Cell Mol. Biol. (American journal of respiratory cell and molecular biology)
[2009, 40(4):474-481]

Cited: 23 times

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Role of sphingosine kinase 1 in allergen-induced pulmonary vascular remodeling and hyperresponsiveness.

Rainer V Haberberger, Christoph Tabeling, Sue Runciman, Birgitt Gutbier, Peter König, Manfred Andratsch, Hartwig Schütte, Norbert Suttorp, Ian Gibbins, Martin Witzenrath,

BACKGROUND: Immunologic processes might contribute to the pathogenesis of pulmonary arterial hypertension (PAH), a fatal condition characterized by progressive pulmonary arterial remodeling, increased pulmonary vascular resistance, and right ventricular failure. Experimental allergen-driven lung inflammation evoked morphologic and functional vascular changes that resembled those observed in patients with PAH. Sphingosine kinase ... Read more >>

J. Allergy Clin. Immunol. (The Journal of allergy and clinical immunology)
[2009, 124(5):933-41.e1-9]

Cited: 11 times

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Role of platelet-activating factor in pneumolysin-induced acute lung injury.

Martin Witzenrath, Birgitt Gutbier, John S Owen, Bernd Schmeck, Timothy J Mitchell, Konstantin Mayer, Michael J Thomas, Satoshi Ishii, Simone Rosseau, Norbert Suttorp, Hartwig Schütte,

OBJECTIVE: Acute respiratory failure is a major complication of severe pneumococcal pneumonia, characterized by impairment of pulmonary microvascular barrier function and pulmonary hypertension. Both features can be evoked by pneumolysin (PLY), an important virulence factor of Streptococcus pneumoniae. We hypothesized that platelet-activating factor (PAF) and associated downstream signaling pathways play ... Read more >>

Crit. Care Med. (Critical care medicine)
[2007, 35(7):1756-1762]

Cited: 15 times

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