Beta2-glycoprotein I as a 'cofactor' for anti-phospholipid reactivity with endothelial cells.
Beta2-glycoprotein I (beta2GPI) is a cofactor for anti-phospholipid (aPL) binding to cardiolipin (CL)-coated plates. Beta2GPI is also able to bind to endothelial cell (EC) membranes as supported by in-vivo as well as by in-vitro studies. The PL-binding site in the fifth domain of the molecule is involved in the adhesion to endothelium. Actually, specific mutations in this molecular portion abolish endothelium binding and a synthetic peptide spanning the sequence Glu274-Cys288 of the CL-binding site displays comparable adhesion to EC monolayers. Heparan sulphate appears to be one of the anionic EC membrane structures with which cationic beta2GPI interacts, as supported by studies with heparitinase-treated EC. Beta2GPI binding to EC might be related to its activity as endothelial growth factor or as a lipid-carrying glycoprotein. Adhesion of beta2GPI to endothelial membranes offers suitable epitopes for circulating aPL that, once bound, can induce cell activation
Meroni
P L
PL
Department of Internal Medicine, IRCCS Policlinico, University of Milan, Italy.
Del Papa
N
N
Raschi
E
E
Panzeri
P
P
Borghi
M O
MO
Tincani
A
A
Balestrieri
G
G
Khamashta
M A
MA
Hughes
G R
GR
Koike
T
T
Krilis
S A
SA
D019943:Amino Acid Substitution; D000838:Anions; D017153:Antibodies, Anticardiolipin / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology*; D001665:Binding Sites; D001777:Blood Coagulation; D002462:Cell Membrane / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D011509:Proteoglycans / Q000378:metabolism; D013499:Surface Properties; D053482:beta 2-Glycoprotein I
D000838:Anions; D017153:Antibodies, Anticardiolipin; D001324:Autoantigens; D000939:Epitopes; D006023:Glycoproteins; D006497:Heparan Sulfate; D046911:Macromolecular Substances; D011509:Proteoglycans; D053482:beta 2-Glycoprotein I