Protein tyrosine kinase involvement in the production of superoxide anion by neutrophils exposed to Aroclor 1242, a mixture of polychlorinated biphenyls.
Biochem Pharmacol
; 53(12): 1833-42, 1997 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-9256158
ABSTRACT
Neutrophils produce superoxide anion (O2-) when exposed in vitro to Aroclor 1242, a mixture of polychlorinated biphenyls (PCBs). The mechanism for this effect shares some similarities with the mechanism by which the physiologic agonist f-Met-Leu-Phe (fMLP) activates neutrophils. Since production of O2- in response to fMLP involves GTP-binding proteins and protein tyrosine kinases (PTKs), the current study was undertaken to determine whether these signalling pathways are involved in PCB-induced neutrophil activation. Neutrophils exposed to Aroclor 1242 or fMLP produced significant O2-. Pretreatment of intact neutrophils with pertussis toxin or cholera toxin or exposure of permeabilized cells to GDPbetaS significantly inhibited O2- production in fMLP-treated neutrophils but did not alter the response to Aroclor 1242. Pretreatment with genistein, an inhibitor of PTKs, significantly inhibited O2- production in both Aroclor 1242- and fMLP-treated neutrophils; however, daidzein, a structural analogue of genistein which lacks activity against PTKs, was without effect. Exposure of neutrophils to Aroclor 1242 resulted in an increase within 1 min in tyrosine phosphorylation of proteins in the 40 and 60 kDa molecular mass ranges which persisted for up to 10 min. Similar results were obtained with 2,2',4,4'-tetrachlorobiphenyl (2,2',4,4'-TCB), a PCB congener that stimulates O2- production. In contrast, 3,3',4,4',5-pentachlorobiphenyl (3,3',4,4',5-PeCB), a congener that does not generate O2-, caused only a transient increase in tyrosine phosphorylation of proteins in the 40 kDa range with no effect on 60 kDa proteins. These data suggest that Aroclor 1242 activates neutrophils to produce O2- by a mechanism that requires tyrosine kinase activity; however, heterotrimeric G-proteins are not likely to be involved.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arocloros
/
Proteínas Tirosina Quinases
/
Bifenilos Policlorados
/
Superóxidos
/
Neutrófilos
Limite:
Animals
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos