Organic peroxides inhibit neutrophil leukotriene B4 biosynthesis.
J Leukoc Biol
; 52(6): 645-51, 1992 Dec.
Article
em En
| MEDLINE
| ID: mdl-1334502
ABSTRACT
Leukotriene B4, an autacoid metabolite of arachidonic acid produced by polymorphonuclear neutrophils, induces chemokinesis, chemotaxis, and adhesion of these cells at sites of inflammation. Because neutrophil infiltration is a self-limited process, we hypothesized that oxidized lipid products of neutrophil-damaged tissue might inhibit leukotriene B4 biosynthesis, thereby preventing additional neutrophil infiltration and limiting peroxidative tissue damage. Erythrocyte ghosts exposed to a hydrogen peroxide-generating system served as a model of peroxidized tissue in inflammation and inhibited neutrophil leukotriene B4 production by 50% compared with unoxidized ghosts. Organic peroxides, including tert-butylhydroperoxide, peracetic acid, and linoleic hydroperoxide, resembling the product(s) of tissue membrane peroxidation in lipid solubility and catalase resistance, inhibited leukotriene B4 biosynthesis in a dose-dependent manner (50% inhibitory concentration of 3.9 microM compared to 530 microM for H2O2). Biosynthetic steps prior to the 5-lipoxygenase did not appear to be the site of inhibition. Likewise, the step after the 5-lipoxygenase, the leukotriene A4 hydrolase, was not primarily involved. Thus a possible mechanism for controlling the influx of neutrophils and their oxidative damage during inflammation may be inhibition of the 5-lipoxygenase by catalase-resistant lipid peroxides released by tissue membranes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Peracético
/
Peróxidos
/
Ácidos Linoleicos
/
Leucotrieno B4
/
Peróxidos Lipídicos
/
Neutrófilos
Limite:
Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
1992
Tipo de documento:
Article