Adenovector-mediated gene transfer of lysophosphatidylcholine acyltransferase 1 attenuates oleic acid-induced acute lung injury in rats.
Crit Care Med
; 42(11): e716-24, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-25319916
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.DESIGN:
Randomized, prospective animal study, including in vitro primary cell culture test.SETTING:
University medical center research laboratory.SUBJECTS:
Adult male Sprague-Dawley rats.INTERVENTIONS:
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. MEASUREMENTS AND MAINRESULTS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Lesão Pulmonar Aguda
/
1-Acilglicerofosfocolina O-Aciltransferase
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Crit Care Med
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Japão