1- O-hexadecyl-2-metoxy-glycero-3-phosphatidylcholine—A methoxy ether lipid inhibiting platelet activating factor-induced platelet aggregation and neutrophil oxidative metabolism

Abstract

Whether or not two alkylglycerols could initiate a functional response in human platelets or modify responses induced by platelet activating factor (PAF) was evaluated. It was found that 1–100 μM 1- O-hexadecyl-2-metoxy-glycero-3-phosphatidylcholine (Et-16-OCH 3) induced platelet aggregation but 1- O-hexadecyl- sn-glycerol (chimyl alcohol; CA) did not. Et-16-OCH 3-induced platelet aggregation was abolished by pretreatment with the PAF receptor antagonist WEB 2086. While CA had no effect on platelet aggregation induced by PAF, pretreatment with Et-16-OCH 3 (0.1 μM or higher) significantly inhibited platelet aggregation induced by PAF, but had no effect on aggregation caused by ADP, thrombin or phorbol myristate acetate (PMA). A receptor binding study using radiolabelled [ 3H]WEB 2086 showed that Et-16-OCH 3 exerts its actions through interaction with the PAF receptor. Moreover, Et-16-OCH 3 inhibited neutrophil chemiluminescence responses induced by PAF, but not reactions to PMA or a formyl peptide. Finally, 1 μM Et-16-OCH 3 induced a rise in the intracellular calcium concentration in platelets equal to that induced by PAF and also had an calcium ionophore-like effect at 100 μM. Thus, this study shows that Et-16-OCH 3 is both a potent inducer of platelet aggregation and an inhibitor of PAF-induced platelet aggregation and neutrophil chemiluminescence, through interaction with the PAF receptor.