期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 192, 期 2, 页码 159-170出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.192.2.159
关键词
eosinophil; asthma; emphysema; alveolar macrophage; adenosine deaminase
资金
- NHLBI NIH HHS [HL61888] Funding Source: Medline
- NIAID NIH HHS [R01 AI043572, AI43572] Funding Source: Medline
- NIDDK NIH HHS [DK46207, R01 DK046207] Funding Source: Medline
Adenosine deaminase (ADA) is a purine catabolic enzyme that manages levels of the biologically active purines adenosine and 2'-deoxyadenosine in tissues and cells. ADA-deficient mice die at 3 wk of age from severe respiratory distress. This phenotype is progressive and is linked to perturbations in pulmonary purine metabolism. The inflammatory changes found in the lungs of ADA-deficient mice included an accumulation of activated alveolar macrophages and eosinophils. These changes were accompanied by a pronounced enlargement of alveolar spaces and increases in mucus production in the bronchial airways. The alveolar enlargement was found to be due in part to abnormal alveogenesis. Lowering adenosine and 2'-deoxyadenosine levels using ADA enzyme therapy decreased the pulmonary eosinophilia and resolved many of the lung histopathologies. In addition, genetically restoring ADA to the forestomach of otherwise ADA-deficient mice prevented adenine metabolic disturbances as well as lung inflammation and damage. These data suggest that disturbances in purinergic signaling mediate the lung inflammation and damage seen in ADA-deficient mice.
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