Effects of pancreatic and snake venom phospholipase A2 on the generation of leukotriene B4 and C4 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 leukocytes 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-induced LTC4 generation. This promoting effect of pancreatic and venom PLA2 required Ca2+ in the incubation medium and was inhibited by mepacrine (10(-5) M). These findings suggest that increased production of PLA2 in combination with inflammatory stimuli such as endotoxin enhance LTB4 biosynthesis in acute pancreatitis.