Author/Editor     Gašperšič, N; Ambrožič, A; Božič, B; Majhenc, J; Svetina, S; Rozman, B
Title     Annexin A5 binding to giant phospholipid vesicles is differentially affected by anti-beta2-glycoprotein I and anti-annexin A5 antibodies
Type     članek
Source     Rheumatol Oxf Print
Vol. and No.     Letnik 46, št. 1
Publication year     2007
Volume     str. 81-6
Language     eng
Abstract     Objectives. Anti-phospholipid antibodies have been recognized to play a role in vascular thrombosis and pregnancy morbidity. They were first thought to be directed to phospholipids, but it is now known that the majority of pathogenic antibodies recognizes epitopes on phospholipid-binding plasma proteins such as beta2-glycoprotein I (beta2GPI) or possibly also annexin A5 (ANXA5). The mechanism of their prothrombotic action is still not completely understood. The aim of the present study was to observe the effect of antibodies against ANXA5 (aANXA5) and antibodies against beta2GPl (abeta2GPI) on the binding of ANXA5 to the negatively charged phospholipid membrane. Methods. Giant phospholipid vesicles (GPVs) were used as a simple model of the membrane surface. GPVs composed of phosphatidylserine and pnosphatidylcholine were produced in an aqueous medium. A single GPV was fransferred fo the solution containing ANXA5 conjugated with Alexa Floor 488 (FANXA5) and (i) aANXA5 or abeta2GPI and (ii) different concentrations of abeta2GPI together with beta2GPl. The emission of the fluorescent light from the GPV surface, as the result of FANXA5 binding, was measured. Results. Beta2GPI together with abeta2GPI reduced the binding of FANXA5 to GPVs. On the contrary, aANXA5 enhanced the binding of ANXA5 to the GPV surface. Conclusions. Our results point to the competition between FANXA5 and complexes of beta2GPI-abeta2GP1 for the same binding sites and therefore support the hypothesis of the disruption of the ANXA5 protective shield on procoagulant phospholipid surface. The influence of increased cell surface ANXA5 concentration in the presence of aANXA5 on coagulation needs to be further studied.
Descriptors     ANNEXIN V
PHOSPHOLIPIDS
PROTEIN BINDING
GLYCOPROTEINS
MEMBRANES, ARTIFICIAL
CALCIUM