Activated scramblase and inhibited aminophospholipid translocase cause phosphatidylserine exposure in a distinct platelet fraction.
Platelet procoagulant activity is mainly determined by the extent of surface-exposed phosphatidylserine (PS), controlled by the activity of aminophospholipid translocase and phospholipid scramblase. Here, we studied both transport activities in single platelets upon stimulation with various agonists. Besides the formation of procoagulant microparticles, the results show that a distinct fraction of the platelets exposes PS when stimulated. The extent of PS exposure in these platelet fractions was similar to that in platelets challenged with Ca2+-ionophore, where all cells exhibit maximal attainable PS exposure. The size of the PS-exposing fraction depends on the agonist and is proportional to the platelet procoagulant activity. Scramblase activity was observed only in the PS-exposing platelet fraction, whereas translocase activity was exclusively detectable in the fraction that did not expose PS. We conclude that, irrespective of the agonist, procoagulant platelets exhibit maximal surface exposure of PS by switching on scramblase and inhibiting translocase activity.
Wolfs
J L N
JL
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Comfurius
P
P
Rasmussen
J T
JT
Keuren
J F W
JF
Lindhout
T
T
Zwaal
R F A
RF
Bevers
E M
EM
D017304:Annexin A5 / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008565:Membrane Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008894:Milk Proteins / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015539:Platelet Activation; D013917:Thrombin / Q000494:pharmacology; D013925:Thromboplastin / Q000378:metabolism
D017304:Annexin A5; D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008565:Membrane Proteins; D008894:Milk Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D015759:Ionomycin; D003094:Collagen; D013925:Thromboplastin; D013917:Thrombin; D016650:Fluorescein-5-isothiocyanate