期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 44, 期 3, 页码 423-429出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2010-0038OC
关键词
P2X(7) receptor; ATP; cigarette smoke-induced lung inflammation; emphysema
资金
- Deutsche Forschungsgemeinschaft [7/4-1]
- Italian Ministry for University and Research, Rome, Italy [2008T5BLWA]
- Nycomed
- Novartis
- Nycomed Pharma
- Neurim
- Boehringer Ingelheim
- Janssen-Cilag
- Astra-Zeneca
- GlaxoSmithKline
- Siemens GmbH
- Nycomed Germany
- Deutsche Forschungsgemeinschaft
- German Ministry for Science and Education
- MSD
- AstraZeneca
- Actelion
- Bayer
- Affectis Pharma AG
- Merck
- Hexal
- Allergopharma
Extracellular ATP is up-regulated in the airways of patients with chronic obstructive pulmonary disease, and may contribute to the pathogenesis of the disease. However, the precise mechanisms are poorly understood. Our objective was to investigate the functional role of the ATP receptor P2X(7) in the pathogenesis of cigarette smoke (CS)-induced lung inflammation and emphysema in vivo. Expression of the P2X(7) receptor (P2X(7)R) was measured in lung tissue und immune cells of mice with CS-induced lung inflammation. In a series of experiments using P2X(7) antagonists and genetically engineered mice, the functional role of the P2X(7)R in CS-induced lung inflammation was explored. CS-induced inflammation was associated with an up-regulation of the P2X(7)R on blood and airway neutrophils, alveolar macrophages, and in whole lung tissue. Selective intrapulmonary inhibition of the P2X(7)R reduced CS-induced lung inflammation and prevented the development of emphysema. Accordingly, P2X(7)R knockout mice showed a reduced pulmonary inflammation after acute CS exposure. Experiments with P2X(7)R chimera animals revealed that immune cell P2X(7)R expression plays an important role in CS-induced lung inflammation and emphysema. Extracellular ATP contributes to the development of CS-induced lung inflammation and emphysema via activation of the P2X(7)R. Inhibition of this receptor may be a new therapeutic target for the treatment of chronic obstructive pulmonary disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据