Back to Search
Start Over
A commercial mixture of the brominated flame retardant pentabrominated diphenyl ether (DE-71) induces respiratory burst in human neutrophil granulocytes in vitro.
- Source :
-
Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2005 Sep; Vol. 87 (1), pp. 57-65. Date of Electronic Publication: 2005 Jun 15. - Publication Year :
- 2005
-
Abstract
- Polybrominated diphenyl ethers (PBDEs) are widely used brominated flame retardants (BFRs), which have become ubiquitous in the environment. This study investigates the effects of the pentabrominated diphenyl ether mixture, DE-71, on human neutrophil granulocytes in vitro. DE-71 enhanced production of reactive oxygen species (ROS) in a concentration-dependent manner measured as lucigenin-amplified chemiluminescence. Octabrominated diphenyl ether (OBDE), decabrominated diphenyl ether (DBDE), and the non-brominated diphenyl ether did not induce ROS formation at the concentrations tested. DPI (4 microM), an inhibitor of the NADPH oxidase completely inhibited DE-71 induced ROS formation, highlighting a role for NADPH oxidase activation. The protein kinase C inhibitor BIM (0.25 microM) and the selective chelator of intracellular calcium, BAPTA-AM (5 microM), also inhibited NADPH oxidase activation, indicating a calcium-dependent activation of PKC. ROS formation was also inhibited by the tyrosine kinase inhibitor tyrphostin (1 microM), the phospholipase C inhibitor ET-18-OCH3 (5 microM), and the phosphatidylinositol-3 kinase inhibitor LY294002 (25 microM). Alterations in intracellular calcium were measured using fura-2/AM, and a significant increase was measured after exposure to DE-71 both with and without extracellular calcium. The tetra brominated compound BDE-47 also enhanced ROS formation in a concentration dependent manner. The combination of DE-71 with the bacteria-derived N-formyl peptide fMLP and PCB153 induced an additive effect in the lucigenin assay. We suggest that tyrosine kinase mediated activation of PI3K could result in enhanced activation of calcium-dependent PKC by enhanced PLC activity, followed by intracellular calcium release leading to ROS formation in neutrophil granulocytes.
- Subjects :
- Adult
Calcium metabolism
Halogenated Diphenyl Ethers
Humans
In Vitro Techniques
Male
N-Formylmethionine Leucyl-Phenylalanine pharmacology
NADPH Oxidases metabolism
Neutrophils metabolism
Phosphatidylinositol 3-Kinases physiology
Reactive Oxygen Species
Signal Transduction
Flame Retardants toxicity
Neutrophils drug effects
Phenyl Ethers toxicity
Polybrominated Biphenyls toxicity
Respiratory Burst drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1096-6080
- Volume :
- 87
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Toxicological sciences : an official journal of the Society of Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 15958660
- Full Text :
- https://doi.org/10.1093/toxsci/kfi222