Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin.

Details

Serval ID
serval:BIB_E429326803E4
Type
Article: article from journal or magazin.
Collection
Publications
Title
Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin.
Journal
Blood
Author(s)
Alberio L., Safa O., Clemetson K.J., Esmon C.T., Dale G.L.
ISSN
0006-4971 (Print)
ISSN-L
0006-4971
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
95
Number
5
Pages
1694-1702
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. Publication Status: ppublish
Abstract
Factor V (FV) present in platelet alpha-granules has a significant but incompletely understood role in hemostasis. This report demonstrates that a fraction of platelets express very high levels of surface-bound, alpha-granule FV on simultaneous activation with 2 agonists, thrombin and convulxin, an activator of the collagen receptor glycoprotein VI. This subpopulation of activated platelets represents 30.7% +/- 4.7% of the total population and is referred to as convulxin and thrombin-induced-FV (COAT-FV) platelets. COAT-FV platelets are also observed on activation with thrombin plus collagen types I, V, or VI, but not with type III. No single agonist examined was able to produce COAT-FV platelets, although ionophore A23187 in conjunction with either thrombin or convulxin did generate this population. COAT-FV platelets bound annexin-V, indicating exposure of aminophospholipids and were enriched in young platelets as identified by the binding of thiazole orange. The functional significance of COAT-FV platelets was investigated by demonstrating that factor Xa preferentially bound to COAT-FV platelets, that COAT-FV platelets had more FV activity than either thrombin or A23187-activated platelets, and that COAT-FV platelets were capable of generating more prothrombinase activity than any other physiologic agonist examined. Microparticle production by dual stimulation with thrombin and convulxin was less than that observed with A23187, indicating that microparticles were not responsible for all the activities observed. These data demonstrate a new procoagulant component produced from dual stimulation of platelets with thrombin and collagen. COAT-FV platelets may explain the unique role of alpha-granule FV and the hemostatic effectiveness of young platelets.
Keywords
Antibodies, Monoclonal/immunology, Blood Coagulation Factors/biosynthesis, Blood Coagulation Factors/immunology, Blood Platelets/drug effects, Blood Platelets/metabolism, Calcimycin/pharmacology, Cell Aging, Cell Membrane/metabolism, Collagen/pharmacology, Crotalid Venoms/pharmacology, Cytoplasmic Granules/enzymology, Hemostasis, Humans, Ionophores/pharmacology, Lectins, C-Type, Membrane Lipids/metabolism, Phospholipids/metabolism, Platelet Activation/drug effects, Proteins/pharmacology, Receptors, Thrombin, Thrombin/pharmacology
Pubmed
Web of science
Create date
10/02/2015 11:06
Last modification date
20/08/2019 16:07
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