» Articles » PMID: 15527422

Quantitative Determination of the Binding of Beta2-glycoprotein I and Prothrombin to Phosphatidylserine-exposing Blood Platelets

Overview
Journal Biochem J
Specialty Biochemistry
Date 2004 Nov 6
PMID 15527422
Citations 4
Authors
Affiliations
Soon will be listed here.
Abstract

The plasma protein beta2GPI (beta2-glycoprotein I) has been proposed to mediate phagocytosis of apoptotic cells and to play a role in the antiphospholipid syndrome. This suggestion is based mainly on the presumption that beta2GPI has an appreciable interaction with PS (phosphatidylserine)-exposing cell membranes. However, quantitative data on the binding of beta2GPI to PS-exposing cells under physiologically relevant conditions are scarce and conflicting. Therefore we evaluated the binding of beta2GPI to PS-expressing blood platelets. Flow cytometry showed that binding of beta2GPI is negligible at physiological ionic strength, in contrast with significant binding occurring at low ionic strength. Binding parameters of beta2GPI and (for comparison) prothrombin were quantified by ellipsometric measurement of protein depletion from the supernatant following incubation with platelets. At low ionic strength (20 mM NaCl, no CaCl2), a dissociation constant (K(d)) of 0.2 microM was found for beta2GPI, with 7.4x10(5) binding sites per platelet. Under physiologically relevant conditions (120 mM NaCl and 3 mM CaCl2), binding of beta2GPI was not detectable (extrapolated K(d)>80 microM). Prothrombin binding (at 3 mM CaCl2) was much less affected by ionic strength: K(d) values of 0.5 and 1.4 muM were observed at 20 and 120 mM NaCl respectively. The low affinity and the presence of many lipid-binding proteins in plasma that can compete with the binding of beta2GPI suggest that only a small fraction (<5%) of the binding sites on PS-exposing blood cells are likely to be occupied by beta2GPI. These findings are discussed in relation to the alleged (patho-)physiological functions of beta2GPI.

Citing Articles

Importance of Efferocytosis in COVID-19 Mortality.

Erol A Infect Drug Resist. 2022; 15:995-1007.

PMID: 35299855 PMC: 8922362. DOI: 10.2147/IDR.S348639.


Anti-β2-glycoprotein I and anti-prothrombin antibodies cause lupus anticoagulant through different mechanisms of action.

Noordermeer T, Molhoek J, Schutgens R, Sebastian S, Drost-Verhoef S, van Wesel A J Thromb Haemost. 2021; 19(4):1018-1028.

PMID: 33421291 PMC: 8048633. DOI: 10.1111/jth.15241.


New insights into the biology and pathobiology of beta2-glycoprotein I.

Giannakopoulos B, Mirarabshahi P, Krilis S Curr Rheumatol Rep. 2010; 13(1):90-5.

PMID: 21089000 DOI: 10.1007/s11926-010-0151-9.


Attachment of beta 2-glycoprotein I to negatively charged liposomes may prevent the release of daughter vesicles from the parent membrane.

Urbanija J, Babnik B, Frank M, Tomsic N, Rozman B, Kralj-Iglic V Eur Biophys J. 2008; 37(7):1085-95.

PMID: 18188552 DOI: 10.1007/s00249-007-0252-1.

References
1.
Thiagarajan P, Le A, Benedict C . Beta(2)-glycoprotein I promotes the binding of anionic phospholipid vesicles by macrophages. Arterioscler Thromb Vasc Biol. 1999; 19(11):2807-11. DOI: 10.1161/01.atv.19.11.2807. View

2.
Rigotti A, Acton S, Krieger M . The class B scavenger receptors SR-BI and CD36 are receptors for anionic phospholipids. J Biol Chem. 1995; 270(27):16221-4. DOI: 10.1074/jbc.270.27.16221. View

3.
Fadok V, Bratton D, Rose D, Pearson A, Ezekewitz R, Henson P . A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature. 2000; 405(6782):85-90. DOI: 10.1038/35011084. View

4.
Ma K, Simantov R, Zhang J, SILVERSTEIN R, Hajjar K, McCrae K . High affinity binding of beta 2-glycoprotein I to human endothelial cells is mediated by annexin II. J Biol Chem. 2000; 275(20):15541-8. DOI: 10.1074/jbc.275.20.15541. View

5.
Savill J, Fadok V . Corpse clearance defines the meaning of cell death. Nature. 2000; 407(6805):784-8. DOI: 10.1038/35037722. View