CORRELATION BETWEEN ARACHIDONIC-ACID OXYGENATION AND LUMINOL-INDUCED CHEMILUMINESCENCE IN NEUTROPHILS - INHIBITION BY DIETHYLDITHIOCARBAMATE

Neutrophils from allergic subjects were hypersensitive to stimulation by low calcium ionophore concentration (0.15 mu M), resulting in an in creased formation of leukotriene B-4 (LTB4), 5S-hydroxy-6,8,11,14-(E,Z ,Z,Z)-eicosatetraenoic acid (5-HETE), and other arachidonic acid metab olites through the 5-lipoxygenase pathway. In parallel, luminol-depend ent chemiluminescence was also higher in neutrophils from allergic pat ients at the basal state and after stimulation by calcium ionophore, r evealing an enhancement of radical oxygen species and peroxide product ion. The activity of glutathione peroxidase, the main enzyme responsib le for hydroperoxide reduction, was lowered in these cells. Diethyl-di thiocarbamate (DTC) induced a concentration-dependent decrease in chem iluminescence and arachidonic acid metabolism after neutrophil stimula tion. These data show that the elevation of arachidonic acid metabolis m in neutrophils from allergic patients is strongly correlated with ox idative status. This elevation may be the consequence of an increased cellular hydroperoxide known to activate 5-lipoxygenase (5-LOX) activi ty and/or an increased arachidonic acid availability, due either to ph ospholipase A(2) (PLA(2)) activation or inhibition of arachidonate ree sterification into phospholipids. Lowering this oxidative status was a ssociated with a concomitant decrease of this metabolism. Our results suggest that the effect of DTC may be the consequence of an inhibition of peroxyl radical and cellular lipid hydroperoxide production. Thus, DTC may modulate arachidonic acid metabolism in neutrophils by modula ting the cellular hydroperoxide level. (C) 1997 Elsevier Science Inc.