Transcellular biosynthesis contributes to the production of leukotrienes during inflammatory responses in vivo.
J Clin Invest
; 109(10): 1373-80, 2002 May.
Article
em En
| MEDLINE
| ID: mdl-12021253
ABSTRACT
Leukotrienes are lipid mediators that evoke primarily proinflammatory responses by activating receptors present on virtually all cells. The production of leukotrienes is tightly regulated, and expression of 5-lipoxygenase, the enzyme required for the first step in leukotriene synthesis, is generally restricted to leukocytes. Arachidonic acid released from the cell membrane of activated leukocytes is rapidly converted to LTA(4) by 5-lipoxygenase. LTA(4) is further metabolized to either LTC(4) or LTB(4) by the enzyme LTC(4) synthase or LTA(4) hydrolase, respectively. Unlike 5-lipoxygenase, these enzymes are expressed in most tissues. This observation previously has led to the suggestion that LTA(4) produced by leukocytes may, in some cases, be delivered to other cell types before being converted into LTC(4) or LTB(4). While in vitro studies indicate that this process, termed transcellular biosynthesis, can lead to the production of leukotrienes, it has not been possible to determine the significance of this pathway in vivo. Using a series of bone marrow chimeras generated from 5-lipoxygenase- and LTA(4) hydrolase-deficient mice, we show here that transcellular biosynthesis contributes to the production of leukotrienes in vivo and that leukotrienes produced by this pathway are sufficient to contribute significantly to the physiological changes that characterize an ongoing inflammatory response.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucotrienos
/
Inflamação
/
Leucócitos
Limite:
Animals
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos