Effects of Calphobindin II (Annexin VI) on procoagulant and Anticoagulant Activities of Cultured Endothelial Cells

• Published in: Chemical & pharmaceutical bulletin Vol. 40; no. 7; pp. 1860 - 1863
• Main Authors: YOSHIZAKI, Hideo, TANABE, Sohei, ARAI, Koichi, MURAKAMI, Akira, WADA, yasushi, OHKUCHI, Masao, HASHIMOTO, Yohichi, MAKI, Masahiro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 1992; Japan Science and Technology Agency
• Subjects: Amino Acid Sequence; Animals; annexin; Annexin A6 - pharmacology; Blood Coagulation - drug effects; calphobindin; Cattle; endothelial cell; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Humans; Molecular Sequence Data; protein C activation; prothrombinase
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.40.1860

Effects of human placental calphobindin II (CPB-II) on the protein C activation and prothrombin activation on the cell surface of cultured calf pulmonary arterial endothelial cells have been investigated. CPB-II inhibited thrombin generation by factor Xa bound to the surface of the cultured endothelial cells in a dose-dependent manner. The amount (IC50) of CPB-II causing the inhibition at 50% was estimated to be approximately 10 nM. CPB-II was found to be ineffective, however, in the protein C activation by thrombin-thrombomodulin (TM) complex on the cell surface. Assay using purified TM revealed that CPB-II was able to exhibit the inhibitory potency for the protein C activation exclusively in the reconstituted system with negatively charged phospholipids. These results suggest that the neutral phospholipids participate in the protein C activation through the thrombin-TM system on the endothelial cell surface. The ability of CPB-II to inhibit procoagulant activity without affecting anticoagulant activity on the cultured endothelial cells is probably related to its potential physiological function, while it is able to exert various degrees of influence upon these activities in blood coagulation by interacting with negatively charged phospholipids in vitro.