Phosphatidylethanolamine Augments Factor Viia-Tissue Factor Activity: Enhancement of Sensitivity to Phosphatidylserine

Pierre F. Neuenschwander, Emma Bianco-Fisher, Alireza R. Rezaie, James H. Morrissey

Research output: Contribution to journalArticlepeer-review


The effect of phosphatidylethanolamine (PE) on the activity of the factor Vlla-tissue factor complex (fVIIa.TF) has been examined with respect to plasma clotting activity and activation of factor X (fX) in a purified system. Vesicles prepared by relipidating membrane-anchored TF (dcTF; TF1-244, lacking the C-terminal cytoplasmic tail) into phospholipid vesicles containing 6 mol % phosphatidylserine (PS) and increasing levels of PE up to 40 mol % (the balance consisting of phosphatidylcholine) were found to progressively shorten TF-initiated clotting in normal human plasma to levels comparable to those observed using dcTF relipidated with cephalin. The shortened clotting times were at least in part due to the ability of PE-containing membranes to better support the activation of fX by the fVIIa.TF complex, as vesicles with increased PE content yielded progressively higher initial rates of fX activation. Surprisingly, PE substantially altered the sensitivity of fX activation to low levels of PS, yielding nearmaximal rates of activation at only 3 mol % PS compared to 15-20 mol % PS required in the absence of PE. The effect of PE was not synergistic with that of PS since PE did not increase fX activation rates at high levels of PS (20 mol %). Examination of the kinetic parameters for fX activation revealed that the majority of the effect of PE was in decreasing the apparent Km for fX. In the absence of PE, values for Km were 4.4µM at 0 mol % PS and 120 nM at 6 mol % PS, whereas in the presence of 40 mol % PE these values were decreased to 650 nM and 41 nM, respectively. Taking into account the plasma concentration of fX (~100 nM), these results strongly suggest that the ability of PE to sensitize the fVIIa. TF complex to low levels of PS may have major repercussions in vivo by enabling various cell surfaces to control fX activation through subtle changes in the composition of the membrane.

Original languageEnglish (US)
Pages (from-to)13988-13993
Number of pages6
Issue number43
StatePublished - Oct 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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