Effect of phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine on the protein C/protein S anticoagulation system.
Phosphatidylserine is known to significantly accelerate the blood coagulation reaction. In a previous communication submitted for publication, we demonstrated that phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine showed effects on the blood coagulation reaction using the factor Xa-prothrombin reaction system, and discuss a new function of membrane phospholipids. The present study examined the role of phospholipids in the blood coagulation regulatory reaction (anticoagulation system), by studying the effects of phospholipids on the protein C/protein S reaction. We have established quantitative methods for measuring activated protein C activity and protein S activity, and used them to measure their activity after the addition of liposomes with different phospholipid compositions. We found that phosphatidylcholine inhibited activated protein C and protein S activities in a dose-dependent manner, as in the factor Xa-prothrombin reaction system. On the other hand, phosphatidylethanolamine and lysophosphatidylcholine showed no effect on activated protein C activity. Phosphatidylethanolamine inhibited and lysophosphatidylcholine accelerated coagulation activity in the factor Xa-prothrombin system, but such effects were not observed in the protein C/protein S reaction system. The coagulation and anticoagulation reactions are exquisitely balanced by thrombin, with a role both as a procoagulant and anticoagulant. Therefore, it is understandable that phosphatidylethanolamine and lysophosphatidylcholine show different effects in the factor Xa-prothrombin and protein C/protein S reaction systems. It appears that coagulation and anticoagulation reactions are co-ordinated and controlled by changes in phospholipid composition of the cellular membrane where the coagulation reaction takes place.
Tsuda
Tomohide
T
Shinotest Corporation, Sagamiharashi, Kanagawa. tomohide.tsuda@shino-test.co.jp
Yoshimura
Hajime
H
Hamasaki
Naotaka
N
D000818:Animals; D002147:Calmodulin; D002417:Cattle; D005165:Factor V / Q000502:physiology; D006487:Hemostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008081:Liposomes / Q000138:chemical synthesis / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry; D011486:Protein C / Q000032:analysis / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017293:Protein S / Q000032:analysis / Q000037:antagonists & inhibitors / Q000187:drug effects*
D002147:Calmodulin; D008081:Liposomes; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011486:Protein C; D017293:Protein S; C483858:phosphatidylethanolamine; D005165:Factor V