EFFECTS OF PANCREATIC AND SNAKE-VENOM PHOSPHOLIPASE-A(2) ON THE GENERATION OF LEUKOTRIENE B-4 AND C-4 BY HUMAN-LEUKOCYTES IN-VITRO

To investigate the effects of phospholipase A2 (PLA2) on leukotriene ( LT) generation, we evaluated LTB4 and LTC4 production by human leukocy tes after incubation with porcine pancreatic and snake venom PLA2. The pancreatic and venom PLA2 did not induce LTB4 and LTC4 generation by human leukocytes alone. However, both types of PLA2 promoted opsonized zymosan-induced LTB4 production in a dose-dependent manner (from 10(- 10) to 10(-8) M), whereas they had no effect on opsonized zymosan-indu ced LTC4 generation. This promoting effect of pancreatic and venom PLA 2 required Ca2+ in the incubation medium and was inhibited by mepacrin e (10(-5) M). These findings suggest that increased production of PLA2 in combination with inflammatory stimuli such as endotoxin enhance LT B4 biosynthesis in acute pancreatitis.