Article abstract
Nature Medicine 13, 913 - 919 (2007)
Published online: 15 July 2007 | doi:10.1038/nm1617
Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells
Marco Idzko1,2, Hamida Hammad1, Menno van Nimwegen1, Mirjam Kool1, Monique A M Willart1, Femke Muskens1, Henk C Hoogsteden1, Werner Luttmann3, Davide Ferrari4, Francesco Di Virgilio4, J Christian Virchow, Jr3 & Bart N Lambrecht1
Abstract
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.
- Department of Pulmonary Medicine, Erasmus University Medical Center, Dr. Molewaterplein 50, P.O. Box 1738, 3000 DR Rotterdan, The Netherlands.
- Department of Pulmonary Medicine, University Hospital Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
- Department of Pulmonary Medicine, University Hospital Rostock, Ernst-Heydemann-Strasse 6, Postfach 10 08 88, 18055 Rostock, Germany.
- Department of Experimental and Diagnostic Medicine, Section of General Pathology, and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Via Borsari 46, I-44100 Ferrara, Italy.
Correspondence to: Marco Idzko1,2 e-mail: marco.idzko@uniklinik-freiburg.de
Correspondence to: Bart N Lambrecht1 e-mail: b.lambrecht@erasmusmc.nl
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