An Essential Role for Lysophosphatidylcholine in the Inhibition of Platelet Aggregation by Secretory Phospholipase

The release of secretory phospholipase A2 (SPLA,) into the mammalian circulation may contribute to the development of hemorrhagic and inflammatory diseases. sPLA, has previously been shown t o alter the behavior of platelets, leukocytes, and endothelial cells, although the molecular basis for these cellular effects has not been established. Our studies indicate that the inhibition of platelet aggregation by snake, bee venom, and pancreatic sPLA, is dependent on a plasma cofactor. This cofactor resides within the lipoprotein fraction of plasma, with 5496,3146, and 11% of the activity present in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low density lipoprotein (VLDL) fractions, respectively. Delipidation of HDL and LDL was associated with the complete loss of platelet-inhibitory activity. Incubation of purified sPLA, with the HDL fraction of plasma resulted in the time-dependent generation of lysophosphatidylcholine