Endothelial cell activation by antiphospholipid antibodies.
Antiphospholipid antibodies are mainly directed against beta 2 glycoprotein I, a phospholipid-binding protein expressed on endothelial cell membranes of different anatomical localizations and recognized by the specific autoantibodies. Antibody binding induces an endothelial activation both in in vitro and in vivo experimental models that might contribute to the prothrombotic state. Endothelial beta 2 glycoprotein I adhesion is mediated by the electrostatic interaction between its cationic phospholipid binding site and anionic structures on the cell membrane; however, binding to annexin II--the endothelial cell receptor for tissue plasminogen activator--plays also a role. Anti-beta-2 glycoprotein I antibodies up-regulate mRNA expression of pro-inflammatory mediators through NF-kappaB translocation and the signaling cascade triggered by Toll-like receptors. Because of the molecular mimicry between beta 2 glycoprotein I and viral/bacterial structures-the natural ligands for Toll-like receptors (TLR)-antibodies might cross-link the molecule associated to the receptors eventually triggering their signaling.
Meroni
P L
PL
Allergy, Clinical Immunology and Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Department of Internal Medicine, University of Milan, Milan, Italy. pierluigi.meroni@unimi.it
Raschi
E
E
Testoni
C
C
Borghi
M O
MO
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology* / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D053482:beta 2-Glycoprotein I