Alpha-tocopherol modulates phosphatidylserine externalization in erythrocytes: relevance in phospholipid transfer protein-deficient mice.
OBJECTIVE
The aim of the present study was to assess the effect of alpha-tocopherol, the main vitamin E isomer on phosphatidylserine (PS) exposure at the surface of circulating erythrocytes, and to determine consequences on erythrocyte properties.


RESULTS
In vitro alpha-tocopherol enrichment of isolated erythrocytes significantly decreased PS externalization as assessed by lower Annexin V-fluorescein isothiocyanate labeling. Plasma phospholipid transfer protein (PLTP) transfers vitamin E, and both alpha- and gamma-tocopherol accumulated in circulating erythrocytes from PLTP-deficient homozygous (PLTP-/-) mice as compared with wild-type mice. In agreement with in vitro studies, vitamin E-enriched erythrocytes from PLTP-/- mice displayed fewer externalized PS molecules than wild-type controls (-64%, P<0.05). The perturbation of phospholipid membrane asymmetry from PLTP-/- erythrocytes was accompanied by impairment of their procoagulant properties, with a 20% increase in clotting time as compared with wild-type controls (P<0.05). Less pronounced, however still significant, changes were observed in alpha-tocopherol content, procoagulant properties, and PS externalization in erythrocytes of PLTP-deficient heterozygotes. Finally, whole blood coagulation and circulating level of D-dimer, which reflects increased thrombus formation in vivo, were significantly decreased in PLTP-/- mice compared with wild-type mice.


CONCLUSIONS
Vitamin E modifies PS externalization in circulating erythrocytes, thus modulating in vivo their PS-dependent procoagulant properties.
Klein
Alexis
A
INSERM U498, IFR100, Université de Bourgogne, Dijon, France.
Deckert
Valérie
V
Schneider
Martina
M
Dutrillaux
Fabienne
F
Hammann
Arlette
A
Athias
Anne
A
Le Guern
Naig
N
Pais de Barros
Jean-Paul
JP
Desrumaux
Catherine
C
Masson
David
D
Jiang
Xian-Cheng
XC
Lagrost
Laurent
L
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology; D002469:Cell Separation; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000502:physiology; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D010641:Phenotype; D010718:Phosphatidylserines / Q000097:blood*; D049294:Phospholipid Transfer Proteins / Q000172:deficiency*; D014914:Whole Blood Coagulation Time; D024502:alpha-Tocopherol / Q000494:pharmacology*
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; C036309:fibrin fragment D; D024502:alpha-Tocopherol