Modulation of leukotriene generation from human polymorphonuclear granulocytes by polychlorinated biphenyls (PCB)

Various isomers of polychlorinated biphenyls (PCB) were studied to induce and modulate the generation of lipo-oxygenase products (leukotrienes) from human polymorphonuclear granulocytes (PMN) under non-cytotoxic conditions. Stimulation of human PMN with PCB did not induce leukotriene generation by themselves, but modulated the subsequent leukotriene formation when opsonized zymosan or sodium fluoride (NaF) were applied as stimuli. The simultaneous addition of PMN with opsonized zymosan and PCB, especially 3,3',4,4'-TCB, led to an increased generation of leukotrienes compared to the control. 3,3',4,4'-TCB exceeded the activity of the remainder PCB in a dose-dependent manner and also induced a chemiluminescence response from PMN. The simultaneous incubation of PMN with NaF and 3,3'-DCB,3,3',4,4'-TCB and 2,2',3,3'-TCB showed an inhibitory effect on leukotriene generation unlike NaF stimulation in the absence of PCB. Incubation of PMN with PCB had no significant effect on leukotriene generation induced by the Ca-ionophore (5 microM). Our data show a direct relationship between the extent of PMN stimulation and the chloro-substitution pattern of the PCB in combination with the different stimuli.