| Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. | |
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MedLine Citation:
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PMID: 17632526 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Extracellular ATP serves as a danger signal to alert the immune system of tissue damage by acting on P2X or P2Y receptors. Here we show that allergen challenge causes acute accumulation of ATP in the airways of asthmatic subjects and mice with experimentally induced asthma. All the cardinal features of asthma, including eosinophilic airway inflammation, Th2 cytokine production and bronchial hyper-reactivity, were abrogated when lung ATP levels were locally neutralized using apyrase or when mice were treated with broad-spectrum P2-receptor antagonists. In addition to these effects of ATP in established inflammation, Th2 sensitization to inhaled antigen was enhanced by endogenous or exogenous ATP. The adjuvant effects of ATP were due to the recruitment and activation of lung myeloid dendritic cells that induced Th2 responses in the mediastinal nodes. Together these data show that purinergic signaling has a key role in allergen-driven lung inflammation that is likely to be amenable to therapeutic intervention. |
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Authors:
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Marco Idzko; Hamida Hammad; Menno van Nimwegen; Mirjam Kool; Monique A M Willart; Femke Muskens; Henk C Hoogsteden; Werner Luttmann; Davide Ferrari; Francesco Di Virgilio; J Christian Virchow; Bart N Lambrecht |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-07-15 |
Journal Detail:
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Title: Nature medicine Volume: 13 ISSN: 1078-8956 ISO Abbreviation: Nat. Med. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-08-07 Completed Date: 2007-10-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9502015 Medline TA: Nat Med Country: United States |
Other Details:
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Languages: eng Pagination: 913-9 Citation Subset: IM |
Affiliation:
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Department of Pulmonary Medicine, Erasmus University Medical Center, Dr. Molewaterplein 50, P.O. Box 1738, 3000 DR Rotterdan, The Netherlands. marco.idzko@uniklinik-freiburg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism*,
pharmacology Animals Asthma / chemically induced, immunology*, metabolism*, pathology Cell Differentiation Dendritic Cells / cytology, drug effects, immunology* Humans Inflammation / chemically induced, immunology, metabolism, pathology Mice Mice, Inbred BALB C Receptors, Purinergic P2 / antagonists & inhibitors, metabolism Suramin / pharmacology Th2 Cells / drug effects, immunology |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Purinergic P2; 145-63-1/Suramin; 56-65-5/Adenosine Triphosphate |
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