Age-related pulmonary emphysema in mice lacking alpha/beta hydrolase domain containing 2 gene.
The alpha/beta hydrolase family genes have been identified as down-regulated genes in human emphysematous lungs. Although proteins in the alpha/beta hydrolase family generally act as enzymes, such as lipases, the specific functions of the Abhd2 protein are unknown. To examine the role of Abhd2 in the lung, we analyzed Abhd2 deficient mice obtained by gene trap mutagenesis. Abhd2 was expressed in the alveolar type II cells. Abhd2 deficiency resulted in a decreased level of phosphatidylcholine in the bronchoalveolar lavage. These mice developed spontaneous gradual progression of emphysema, due to increased macrophage infiltration, increased inflammatory cytokines, a protease/anti-protease imbalance and enhanced apoptosis. This phenotype is more akin to the pace of emphysema that develops in humans. Our findings suggest that derangement in alveolar phospholipid metabolism can induce emphysema, and that Abhd2 plays a critical role in maintaining lung structural integrity.
Jin
Shoude
S
Department of Gerontology, Shengjing Hospital, China Medical University, Sanhao Street 36, Heping Ward, Shenyang 110004, China.
Zhao
Gang
G
Li
Zhenghua
Z
Nishimoto
Yuki
Y
Isohama
Yoichiro
Y
Shen
Jingling
J
Ito
Takaaki
T
Takeya
Motohiro
M
Araki
Kimi
K
He
Ping
P
Yamamura
Ken-ichi
K
D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D006867:Hydrolases / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D016877:Oxidants / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000235:genetics* / Q000473:pathology*
D000975:Antioxidants; D016207:Cytokines; D016877:Oxidants; D010743:Phospholipids; D011506:Proteins; D006867:Hydrolases; C454240:Abhd2 protein, mouse; D010447:Peptide Hydrolases