Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice.
J Exp Med
; 181(2): 569-75, 1995 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-7836912
ABSTRACT
Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Fosfatídicos
/
Transdução de Sinais
/
Citocinas
/
Hemorragia
/
Inflamação
/
Pulmão
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
1995
Tipo de documento:
Article