Activation of phospholipases A1 and A2 in heart, liver, and blood during endotoxin shock

The effects of endotoxin shock on the activities of phospholipases A1 and A2 were studied in canine heart sarcolemma, liver plasma membrane, and blood serum. Results obtained from control dogs indicate that phospholipases A1 and A2 were equally active in cardiac sarcolemma. In liver plasma membrane the activity of phospholipase A1 was twice that of phospholipase A2, while in blood serum phospholipase A1 activity was only half that of phospholipase A2. Results obtained 4 hr after endotoxin administration (0.5 mg/kg, iv) demonstrate that phospholipase A1 activities were activated by 117% in cardiac sarcolemma, 188% in liver plasma membrane, and 150% in blood serum, while phospholipases A2 activities were stimulated by 71% in cardiac sarcolemma, 175% in liver plasma membrane, and 31% in blood serum. The in vitro incubation of all three enzyme preparations from control dogs with endotoxin (5-15 micrograms/0.5 ml) stimulated both phospholipase A1 and A2 activities and the stimulation was concentration dependent. These data suggest that endotoxin may have a direct stimulatory effect on phospholipases A1 and A2 activities in the cell membranes of heart and liver, and also in blood serum. Since phospholipases A play an important role in the regulation of membrane structure and function, the observed activation of phospholipases A1 and A2 may have a physiological significance in the pathogenesis of cellular dysfunction in endotoxin shock.