Enhanced inhibition of tissue factor by the extended form of an endothelial cell glycoprotein (an extrinsic pathway inhibitor).
We have identified, in the supernatant medium of cultured endothelial cells, an additional inhibitor of tissue factor that is eluted at higher salt concentrations during heparin-Sepharose chromatography and is a much more potent inhibitor of the activation of the coagulation cascade than the species we studied earlier (Colburn and Buonassisi: In Vitro Cellular and Developmental Biology 24: 1133-1136, 1988). The inhibitor we described earlier has been shown to be functionally and immunologically identical to a rabbit plasma extrinsic pathway inhibitor, EPI (Warn-Cramer et al.: Thrombosis Research 61:515-527, 1991). The new species (molecular mass, 47 kDa) is susceptible to proteolytic cleavage which results in a sharp reduction of its ability to inhibit tissue factor and an increase in electrophoretic mobility compatible with a molecular mass of 45 kDa, the same as that of the inhibitor reported earlier. Based on these data, we suggest that the new inhibitor yields, through proteolytic cleavage of an amino acid sequence of about 25 residues, the N-glycan-sulfated compound previously described.
Colburn
P
P
W.A.J. Cell Science Center, Lake Placid, New York 12946.
Crabb
J W
JW
Buonassisi
V
V
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular; D005167:Factor VII / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D065427:Factor Xa Inhibitors; D006031:Glycosylation; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology
D065427:Factor Xa Inhibitors; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII; D013925:Thromboplastin