The role of phospholipid transfer protein in lipoprotein-mediated neutralization of the procoagulant effect of anionic liposomes.
BACKGROUND
Serum has the ability to neutralize the procoagulant properties of anionic liposomes, with transfer of phospholipids (PLs) to both high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. Phospholipid transfer protein (PLTP) mediates transfer of PLs between HDL and other lipoproteins and conversion of HDL into larger and smaller particles.


OBJECTIVE
To examine the role of PLTP in the neutralization of procoagulant liposomes.


METHODS
Procoagulant liposomes were incubated with different lipoproteins in the presence or absence of PLTP, and then tested for their ability to stimulate thrombin formation.


CONCLUSIONS
In the absence of added PLTP, the lipoprotein-enriched fraction, total HDL, HDL(3) and very high-density lipoprotein (VHDL) were all able to neutralize the procoagulant properties of the liposomes. In these samples, endogenous PLTP was present, as judged by Western blotting. In contrast, no PLTP was present in LDL, HDL(2) and lipoprotein-deficient serum, all of which displayed no ability to neutralize the procoagulant liposomes. The phospholipid (PL) transfer activity was dependent on both enzyme (PLTP) and PL acceptor (lipoproteins). After treatment of the VHDL fraction with antiserum against PLTP, the neutralization of procoagulant activity was reduced, but could be regained by the addition of active PLTP. The neutralizing activity was dependent on a catalytically active form of PLTP, and addition of a low activity form of PLTP had no effect. In conclusion, PLTP was found to mediate transfer of anionic PLs to HDL and LDL, thereby neutralizing the effect of procoagulant liposomes, resulting in a reduction of procoagulant activity.
Oslakovic
C
C
Department of Laboratory Medicine, Division of Clinical Chemistry, Lund University, University Hospital, Malmö, Sweden.
Jauhiainen
M
M
Ehnholm
C
C
Dahlbäck
B
B
D000838:Anions; D001777:Blood Coagulation; D015153:Blotting, Western; D004789:Enzyme Activation; D006801:Humans; D047468:Immunoprecipitation; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008081:Liposomes; D049294:Phospholipid Transfer Proteins / Q000097:blood*; D010743:Phospholipids / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*
D000838:Anions; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008081:Liposomes; C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; C026277:very high density lipoproteins; D013917:Thrombin