Abstract | BACKGROUND: OBJECTIVE: METHODS: SphK1-deficient mice and C57Bl/6 littermates (wild-type [WT] animals) were subjected to acute or chronic allergen exposure. RESULTS: After 4 weeks of systemic ovalbumin sensitization and local airway challenge, airway responsiveness increased less in SphK1(-/-) compared with WT mice, whereas pulmonary vascular responsiveness was greatly increased and did not differ between strains. Acute lung inflammation led to an increase in eosinophils and mRNA expression for S1P phosphatase 2 and S1P lyase in lungs of WT but not SphK1(-/-) mice. After repetitive allergen exposure for 8 weeks, airway responsiveness was not augmented in SphK1(-/-) or WT mice, but pulmonary vascular responsiveness was increased in both strains, with significantly higher vascular responsiveness in SphK1(-/-) mice compared with that seen in WT mice. Increased vascular responsiveness was accompanied by remodeling of the small and intra-acinar arteries. CONCLUSION: : The data support a role for SphK1 and S1P in allergen-induced airway inflammation. However, SphK1 deficiency increased pulmonary vascular hyperresponsiveness, which is a component of PAH pathobiology. Moreover, we show for the first time the dissociation between inflammation-induced remodeling of the airways and pulmonary vasculature.
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Authors | Rainer V Haberberger, Christoph Tabeling, Sue Runciman, Birgitt Gutbier, Peter König, Manfred Andratsch, Hartwig Schütte, Norbert Suttorp, Ian Gibbins, Martin Witzenrath |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 124
Issue 5
Pg. 933-41.e1-9
(Nov 2009)
ISSN: 1097-6825 [Electronic] United States |
PMID | 19665772
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Allergens
- Cytokines
- Lysophospholipids
- RNA, Messenger
- sphingosine 1-phosphate
- Ovalbumin
- Phosphotransferases (Alcohol Group Acceptor)
- sphingosine kinase
- Sphingosine
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Topics |
- Acute Disease
- Allergens
(immunology)
- Animals
- Bronchial Hyperreactivity
(chemically induced, immunology)
- Chronic Disease
- Cytokines
(biosynthesis, immunology)
- Hypertension, Pulmonary
(enzymology, immunology, pathology)
- Lung
(metabolism, pathology)
- Lysophospholipids
(biosynthesis)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Ovalbumin
(immunology)
- Phosphotransferases (Alcohol Group Acceptor)
(genetics, immunology, metabolism)
- Pulmonary Artery
(enzymology, immunology, pathology)
- RNA, Messenger
(immunology, metabolism)
- Sphingosine
(analogs & derivatives, biosynthesis)
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