Ortho-substituted polybrominated biphenyls activate respiratory burst in granulocytes from humans.

The in vivo consequences of exposure to polychlorinated biphenyls (PCB) have been reported to involve reduced phagocytic function, which could be related to increased susceptibility to infections. Though less abundant in the environment, polybrominated biphenyls (PBB) have similar toxicological properties as PCB. In this respect the effect of different PBBs on human granulocytes was elucidated. Ortho-substituted PBBs activated respiratory burst, measured by the chemiluminescence assay, and elevated intracellular calcium. The most active polybrominated congener 2,2',5-TBB increased chemiluminescence in a concentration-dependent manner, and ED(50) was approximately 10 microM. PBBs stimulated elevation of intracellular [Ca(2+)] in human granulocytes. The [Ca(2+)]i was elevated from 50 to 250 nM. The respiratory burst due to stimulation by PBBs was inhibited by U73122, ethanol (1%), wortmannin, and bisindolylmaleimide and by the elimination of extracellular calcium in the same way as shown previously for PCBs, indicating that PBB act by the same mechanisms.

The effect of various substituents in ortho position of biphenyls on respiratory burst, intracellular calcium elevation in human granulocytes, and uptake of dopamine into rat brain synaptic vesicles and synaptosomes.

Polychlorinated biphenyls (PCBs) are a group of compounds, which have effects on the immune and nervous system. We have investigated the effects of seven diortho-substituted biphenyls with different substituents on activation of respiratory burst and calcium elevation in human granulocytes, and inhibition of the uptake of dopamine into synaptic vesicles and synaptosomes isolated from rat brain. We have attempted to find the chemical and physical properties, which can contribute to the variation in biological effects. These properties include the absolute hardness, the molecular size, the hydrophobicity of the molecules, the retention time on a DB5-MS GC-column and the electronegativity of the substituents. In general the dichloro- and dibromobiphenyls were the most potent in all biological tests. The difluorosubstituted was less potent than the other two halide-biphenyls presumably because of the smaller size of the substituent. Dimethylbiphenyl was active in all tests. Dihydroxy- and dimethanolbiphenyl were inactive in all tests, whereas dinitrobiphenyl was only active as a vesicular dopamine uptake inhibitor. Important physico-chemical parameters correlated to the effects were absolute hardness, molecular size and lipophilicity. Among the tested diortho-substituted biphenyls the most active were the chlorinated, brominated, and methylated. This indicates the significance of the molecular size in combination with the hydrophobicity for the studied toxic effects.