title: Age-related pulmonary emphysema in mice lacking alpha/beta hydrolase domain containing 2 gene.
abstract: 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.
authors.affiliation: Department of Gerontology, Shengjing Hospital, China Medical University, Sanhao Street 36, Heping Ward, Shenyang 110004, China.
authors.forename: Shoude
authors.initials: S
authors.lastname: Jin
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Li
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nishimoto
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Isohama
authors.forename: Jingling
authors.initials: J
authors.lastname: Shen
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamamura
mesh_terms: 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*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D016877:Oxidants; D010743:Phospholipids; D011506:Proteins; D006867:Hydrolases; C454240:Abhd2 protein, mouse; D010447:Peptide Hydrolases