title: Adenovector-mediated gene transfer of lysophosphatidylcholine acyltransferase 1 attenuates oleic acid-induced acute lung injury in rats.
abstract: OBJECTIVE
  Lysophosphatidylcholine is generated through the hydrolysis of phosphatidylcholine by phospholipase A2 and reversely converted to phosphatidylcholine by lysophosphatidylcholine acyltransferase 1. Although lysophosphatidylcholine is a potent proinflammatory mediator and increased in several types of acute lung injuries, the role of lysophosphatidylcholine acyltransferase 1 has not yet been addressed. We aimed to investigate whether the exogenous expression of lysophosphatidylcholine acyltransferase 1 could attenuate acute lung injury.
  
  
  METHODS
  Randomized, prospective animal study, including in vitro primary cell culture test.
  
  
  METHODS
  University medical center research laboratory.
  
  
  METHODS
  Adult male Sprague-Dawley rats.
  
  
  METHODS
  Recombinant adenoviruses carrying complementary DNA encoding lysophosphatidylcholine acyltransferase 1 or lacZ (Ad-lacZ) as a control was constructed. Alveolar type II cells were isolated from rats and cultured on tissue-culture inserts. Rats were pretreated with an endobronchial administration of the recombinant adenovirus. One week later, they were IV injected with oleic acid. The lungs were examined 4 hours post oleic acid.
  
  
  RESULTS
  Adenoviruses carrying complementary DNA encoding lysophosphatidylcholine acyltransferase 1-infected alveolar type II cells showed lower lysophosphatidylcholine levels and a decreased percentage of cell death compared with Ad-lacZ-infected cells or noninfected cells after exposure to hydrogen peroxide for 1 hour. Compared with Ad-lacZ plus oleic acid-treated lungs, adenoviruses carrying complementary DNA encoding lysophosphatidylcholine acyltransferase 1 plus oleic acid-treated lungs showed a lower wet-to-dry lung weight ratio, a higher lung compliance, lower lysophosphatidylcholine contents, higher phosphatidylcholine contents, and a lower apoptosis ratio of alveolar type II cells. Histological scoring revealed that the adenoviruses carrying complementary DNA encoding lysophosphatidylcholine acyltransferase 1-treated lungs developed oleic acid-induced lung injuries that were attenuated compared with those of Ad-lacZ-treated lungs.
  
  
  CONCLUSIONS
  Exogenous expression of lysophosphatidylcholine acyltransferase 1 protects alveolar type II cells from oxidant-induced cell death in vitro, and endobronchial delivery of a lysophosphatidylcholine acyltransferase 1 transgene effectively attenuates oleic acid-induced acute lung injury in vivo. These results suggest that lysophosphatidylcholine acyltransferase 1 plays a protective role in acute lung injury.
authors.affiliation: 1Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, Japan. 2Research Institute of Respiratory Diseases, Department of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 3Department of Microbiology, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Osanai
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Taku
authors.initials: T
authors.lastname: Oikawa
authors.forename: Ken
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Mizuno
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Muraki
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Toga
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000235:genetics / Q000494:pharmacology*; D055371:Acute Lung Injury / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D000256:Adenoviridae; D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D008297:Male; D019301:Oleic Acid / Q000009:adverse effects / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
chemical_list: D019301:Oleic Acid; D008243:1-Acylglycerophosphocholine O-Acyltransferase