Budding, vesiculation and permeabilization of phospholipid membranes-evidence for a feasible physiologic role of beta2-glycoprotein I and pathogenic actions of anti-beta2-glycoprotein I antibodies.
The in vivo physiologic role of beta2-glycoprotein I (beta2GPI) is presumed to be related to its interactions with negatively charged phospholipid membranes. Increased quantities of procoagulant microparticles derived by the vesiculation of blood cells have been detected in patients with antiphospholipid syndrome (APS) frequently associated with antibodies against beta2GPI (anti-beta2GPI). We investigated the influence of beta2GPI and anti-beta2GPI on giant phospholipid vesicles (GPVs). GPVs composed of phosphatidylserine and phosphatidylcholine were formed in an aqueous medium and individually transferred to a compartment containing either beta2GPI, anti-beta2GPI, or beta2GPI along with anti-beta2GPI. Shape changes of a single GPV were observed by a phase contrast microscope. Most GPVs transferred to the solution containing only beta2GPI budded moderately. Upon the transfer of GPVs to the solution containing beta2GPI and anti-beta2GPI either from patient with APS or mouse monoclonal anti-beta2GPI Cof-22, the budding was much more pronounced, generating also daughter vesicles. No such effects were seen when GPV was transferred to the solution containing anti-beta2GPI without beta2GPI. Our results suggest a significant physiologic role of beta2GPI in the budding of phospholipid membranes, which may be explained by the insertion of the C-terminal loop of beta2GPI into membranes, thus increasing the surface of the outer layer of a phospholipid bilayer. Anti-beta2GPI, recognizing domains I to IV of beta2GPI, enhanced the budding and vesiculation of GPVs in the presence of beta2GPI. This might be a novel pathogenic mechanism of anti-beta2GPI, promoting in vivo the expression of proadhesive and procoagulant phospholipid surfaces in APS.
Ambrozic
Ales
A
Department of Rheumatology, University Medical Centre, Vodnikova 62, 1000 Ljubljana, Slovenia. ales.ambrozic@mf.uni-lj.si
Bozic
Borut
B
Kveder
Tanja
T
Majhenc
Janja
J
Arrigler
Vesna
V
Svetina
Sasa
S
Rozman
Blaz
B
D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000502:physiology; D022162:Cytoplasmic Vesicles / Q000187:drug effects* / Q000648:ultrastructure; D006023:Glycoproteins / Q000276:immunology* / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000502:physiology*; D008566:Membranes / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D010743:Phospholipids; D053482:beta 2-Glycoprotein I