Endothelial cells as target for antiphospholipid antibodies. Human polyclonal and monoclonal anti-beta 2-glycoprotein I antibodies react in vitro with endothelial cells through adherent beta 2-glycoprotein I and induce endothelial activation.
OBJECTIVE
To investigate the ability of human anti-beta 2-glycoprotein I (anti-beta 2 GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions.


METHODS
Six human affinity-purified polyclonal anti-beta 2 GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphospholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent beta 2 GPI and 2) modulate endothelial adhesion molecule expression and interleukin-6 (IL-6) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) secretion.


RESULTS
The affinity-purified IgG and the MAb with anti-beta 2 GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum-free medium and was restored in a dose-dependent manner by exogenous human beta 2 GPI. After EC binding, both polyclonal and monoclonal antibodies up-regulated adhesion molecule expression. Anti-beta 2 GPI MAb also significantly increased IL-6 and 6-keto-PGF1 alpha secretion.


CONCLUSIONS
These findings support the hypothesis that anti-beta 2 GPI antibodies bind and activate EC through the adherent cofactor beta 2 GPI, likely leading to a procoagulant state.
Del Papa
N
N
University of Milan, Italy.
Guidali
L
L
Sala
A
A
Buccellati
C
C
Khamashta
M A
MA
Ichikawa
K
K
Koike
T
T
Balestrieri
G
G
Tincani
A
A
Hughes
G R
GR
Meroni
P L
PL
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000097:blood; D001053:Apolipoproteins / Q000097:blood / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D000939:Epitopes; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D011485:Protein Binding; D014471:Umbilical Veins / Q000166:cytology; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D001053:Apolipoproteins; D015815:Cell Adhesion Molecules; D000939:Epitopes; D006023:Glycoproteins; D007074:Immunoglobulin G; D015850:Interleukin-6; D053482:beta 2-Glycoprotein I; D015121:6-Ketoprostaglandin F1 alpha