Presentation is loading. Please wait.

Presentation is loading. Please wait.

Role of sphingosine kinase 1 in allergen-induced pulmonary vascular remodeling and hyperresponsiveness  Rainer V. Haberberger, PhD, Christoph Tabeling,

Published byCalvin Ethelbert Hoover Modified over 6 years ago

Similar presentations

Presentation on theme: "Role of sphingosine kinase 1 in allergen-induced pulmonary vascular remodeling and hyperresponsiveness  Rainer V. Haberberger, PhD, Christoph Tabeling,"— Presentation transcript:

1 Role of sphingosine kinase 1 in allergen-induced pulmonary vascular remodeling and hyperresponsiveness  Rainer V. Haberberger, PhD, Christoph Tabeling, Sue Runciman, PhD, Birgitt Gutbier, Peter König, MD, Manfred Andratsch, PhD, Hartwig Schütte, MD, Norbert Suttorp, MD, Ian Gibbins, PhD, Martin Witzenrath, MD  Journal of Allergy and Clinical Immunology  Volume 124, Issue 5, Pages e9 (November 2009) DOI: /j.jaci Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Acute allergen-induced inflammation. Airway resistance (resaw; A), airway responsiveness to MCh infusion (B), Ppa (C), and pulmonary vascular responsiveness to infused U46619 (D) were monitored in isolated perfused and ventilated murine lungs. BAL fluid leukocytes were counted and analyzed by means of microscopic analysis (E). Values are shown as means ± SEMs (WT mice: n = per group; SphK1−/− mice: n = 8-9 per group). ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001 versus corresponding PBS/OVA or as indicated. #P < .05. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Chronic allergen-induced inflammation. Airway resistance (resaw; A), airway responsiveness to MCh infusion (B), Ppa (C), and pulmonary vascular responsiveness to infused U46619 (D) were monitored in isolated perfused and ventilated murine lungs. BAL fluid leukocytes were counted and analyzed by means of microscopic analysis (E). Values are shown as means ± SEMs (WT mice: n = 10 per group; SphK1−/− mice: n = 7-9 per group). ##P < .01 and ∗∗∗P < .001 versus corresponding PBS/OVA-treated group. &P < .05 versus the WT PBS/OVA-treated group). Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Pulmonary cytokine production was quantified in BAL supernatants by using the cytokine multiplex assay. Values are shown as means ± SEMs (n = 5-8 per group). P/O, PBS/OVA; O/O, OVA/OVA. ∗P < .05, ∗∗P < .01, and ∗∗∗P < Dotted lines indicate the detection limit of the cytokine assay and are missing if all values were within the working range. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Chronic allergen-induced lung inflammation (A-F). Histochemistry of small pulmonary arteries (hematoxylin and eosin staining [Fig 4, A and B]) and double-labeling immunohistochemistry (α–smooth muscle actin [α-SMA] green/CD68 red [Fig 4, C-F]; α-SMA green/Ki67 red [Fig 4, G and H]) of intra-acinar arteries in lungs from SphK1−/− mice (Fig 4, A and E) and WT mice (Fig 4, B and F) after OVA/OVA treatment are shown. Fig 4, C and D, show intra-acinar arteries of the SphK1−/− and WT PBS/OVA-treated groups. Acute allergen-induced lung inflammation is shown in Fig 4, G and H. Ki67-immunoreactive nuclei were found in smooth muscle cells of the SphK1−/− (Fig 4, G) and WT (Fig 4, H) OVA/OVA-treated groups. These photomicrographs are representative of 3 to 5 mice examined per group. Bars = 50 μm (Fig 4, A-F); 20 μm (Fig 4, G and H). Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Chronic allergen-induced lung inflammation (n = 6-9 per group.). A, Quantitative morphometric analysis: volume density of vascular walls in small pulmonary arteries and intra-acinar arteries in SphK1−/− and WT mice after PBS/OVA or OVA/OVA treatment. B, Regression analysis of the vascular responsiveness to U46619 and the volume density of small pulmonary arterial walls in SphK1−/− and WT mice. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 Immunohistochemistry (A-C), toluidine blue staining (D and E), and ultrastructural analysis (D′ and E′) of arteries from SphK1−/− mice (Fig 6, C and D) showed the presence of α–smooth muscle actin–immunoreactive smooth muscle cells luminal to the internal elastic lamina (arrows in Fig 6, A and B). Fig 6, C, shows a different orientation of smooth muscle cells in the media and intimal layer. OVA/OVA (Fig 6, E and E′) but not PBS/OVA (Fig 6, D and D′) arteries of SphK1−/− mice contained smooth muscle (sm) luminal to the internal elastic lamina (arrows). Note the increased thickness of the internal elastic lamina in chronic challenged arteries (Fig 6, E′). ec, Endothelial cells. These photomicrographs are representative for 3 to 5 mice examined per group. Bars: 50 μm (Fig 6, A-C); 5 μm (Fig 6, D′ and E′). Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Effect of age on pulmonary vascular responsiveness to infused U46619 was analyzed in isolated perfused and ventilated lungs of 10-week-old (10 w), 14-week-old (14 w), and 18-week-old (18 w) SphK1−/− and WT mice. Values are shown as means ± SEMs (n = 5-7 per group). Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Quantitative RT-PCR analysis: A-C, acute allergen-induced lung inflammation; D, chronic allergen-induced lung inflammation. Acute allergen challenge led to upregulation of S1PP2 (Fig E2, A) and S1Ply (Fig E2, B) mRNA in WT mice but not in SphK1−/− mice. Acute inflammation induced downregulation of SphK2 and S1P1 mRNA in lungs from SphK1−/− mice (Fig E2, C), whereas chronic inflammation reduced S1P1 mRNA in lungs from SphK1−/− mice (Fig E2, D). The data represent 5 to 7 lungs per group. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Ultrastructural analysis of WT (A and B) and SphK1−/− (C and D) capillary endothelium showed the presence of enlarged luminal spaces between cells in OVA/OVA-treated (arrows in Fig E3, B and D) but not PBS/OVA-treated (Fig E3, A and C) arteries. These photomicrographs are representative of 3 to 5 mice examined per group. Bars = 200 nm. Journal of Allergy and Clinical Immunology  , e9DOI: ( /j.jaci ) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Download ppt "Role of sphingosine kinase 1 in allergen-induced pulmonary vascular remodeling and hyperresponsiveness  Rainer V. Haberberger, PhD, Christoph Tabeling,"

Similar presentations

Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore–induced allergic airway disease  Ana Paula Moreira, PhD, Karen A.

Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore–induced allergic airway disease  Ana Paula Moreira, PhD, Karen A.
Sejal Saglani, MD, Stephen Lui, PhD, Nicola Ullmann, MD, Gaynor A

Sejal Saglani, MD, Stephen Lui, PhD, Nicola Ullmann, MD, Gaynor A
Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma  Kyung S. Lee, MS, Sun M. Jin,

Doxycycline reduces airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate–induced asthma  Kyung S. Lee, MS, Sun M. Jin,
Effective prevention and therapy of experimental allergic asthma using a GATA-3– specific DNAzyme  Serdar Sel, MD, Michael Wegmann, PhD, Tanja Dicke, MSc,

Effective prevention and therapy of experimental allergic asthma using a GATA-3– specific DNAzyme  Serdar Sel, MD, Michael Wegmann, PhD, Tanja Dicke, MSc,
Airway microbiome and responses to corticosteroids in corticosteroid-resistant asthma patients treated with acid suppression medications  Elena Goleva,

Airway microbiome and responses to corticosteroids in corticosteroid-resistant asthma patients treated with acid suppression medications  Elena Goleva,
Increased TGF-β2 in severe asthma with eosinophilia

Increased TGF-β2 in severe asthma with eosinophilia
Frank Kirstein, PhD, Natalie E

Frank Kirstein, PhD, Natalie E
Maternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring  Phoebe K. Richgels, MS, Amnah.

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring  Phoebe K. Richgels, MS, Amnah.
Compartmentalized chemokine-dependent regulatory T-cell inhibition of allergic pulmonary inflammation  Roshi Afshar, PhD, James P. Strassner, BS, Edward.

Compartmentalized chemokine-dependent regulatory T-cell inhibition of allergic pulmonary inflammation  Roshi Afshar, PhD, James P. Strassner, BS, Edward.
Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction  Marta Kaminska, MD, Susan Foley, MD, Karim Maghni,

Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction  Marta Kaminska, MD, Susan Foley, MD, Karim Maghni,
IL-33 dysregulates regulatory T cells and impairs established immunologic tolerance in the lungs  Chien-Chang Chen, PhD, Takao Kobayashi, PhD, Koji Iijima,

IL-33 dysregulates regulatory T cells and impairs established immunologic tolerance in the lungs  Chien-Chang Chen, PhD, Takao Kobayashi, PhD, Koji Iijima,
Restoration of T-box–containing protein expressed in T cells protects against allergen- induced asthma  Jung Won Park, MD, Hyun Jung Min, MS, Jung Ho Sohn,

Restoration of T-box–containing protein expressed in T cells protects against allergen- induced asthma  Jung Won Park, MD, Hyun Jung Min, MS, Jung Ho Sohn,
IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin  Robert J. Salmond, PhD, Ananda S. Mirchandani,

IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin  Robert J. Salmond, PhD, Ananda S. Mirchandani,
Leukocyte nicotinamide adenine dinucleotide phosphate-reduced oxidase is required for isocyanate-induced lung inflammation  Si-Yen Liu, PhD, Wei-Zhi Wang,

Leukocyte nicotinamide adenine dinucleotide phosphate-reduced oxidase is required for isocyanate-induced lung inflammation  Si-Yen Liu, PhD, Wei-Zhi Wang,
Allergic airway disease is unaffected by the absence of IL-4Rα–dependent alternatively activated macrophages  Natalie E. Nieuwenhuizen, PhD, Frank Kirstein,

Allergic airway disease is unaffected by the absence of IL-4Rα–dependent alternatively activated macrophages  Natalie E. Nieuwenhuizen, PhD, Frank Kirstein,
Is 9 more than 2 also in allergic airway inflammation?

Is 9 more than 2 also in allergic airway inflammation?
Responsiveness to respiratory syncytial virus in neonates is mediated through thymic stromal lymphopoietin and OX40 ligand  Junyan Han, PhD, Azzeddine.

Responsiveness to respiratory syncytial virus in neonates is mediated through thymic stromal lymphopoietin and OX40 ligand  Junyan Han, PhD, Azzeddine.
Eosinophils contribute to the resolution of lung-allergic responses following repeated allergen challenge  Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,

Eosinophils contribute to the resolution of lung-allergic responses following repeated allergen challenge  Katsuyuki Takeda, MD, PhD, Yoshiki Shiraishi,
Signaling through FcRγ-associated receptors on dendritic cells drives IL-33–dependent TH2-type responses  Melissa Y. Tjota, BA, Cara L. Hrusch, PhD, Kelly.

Signaling through FcRγ-associated receptors on dendritic cells drives IL-33–dependent TH2-type responses  Melissa Y. Tjota, BA, Cara L. Hrusch, PhD, Kelly.
Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology  Carla P. Jones, PhD, Lisa G. Gregory, PhD, Benjamin Causton, BSc, Gaynor A.

Activin A and TGF-β promote TH9 cell–mediated pulmonary allergic pathology  Carla P. Jones, PhD, Lisa G. Gregory, PhD, Benjamin Causton, BSc, Gaynor A.

Similar presentations

Ads by Google