Evidence for anticoagulant activity and beta2-GPI accumulation in late endosomes of endothelial cells induced by anti-LBPA antibodies.
This investigation was undertaken to test whether anti-LBPA antibodies and IgG from patients with APS interfere with intracellular beta2GPI distribution in EAhy926 endothelial cells and with the coagulation system. Cell incubation with anti-LBPA MoAb or with patients' IgG resulted in antibody binding to late endosomes and caused beta2GPI redistribution and accumulation within perinuclear vesicular structures reminiscent of late endosomes. This finding suggests that aPI may contribute to the pathogenic mechanisms of APS by modifying the intracellular traffic of proteins, by interactions between aPl and LBPA, beta2GPI and/or LBPA-beta2GPI complexes. The anticoagulant activity of anti-LBPA MoAb was analyzed in a sensitized activated partial thromboplastin time (aPTT) system and in a dilute Russell's viper venom time (dRVVT). A significant, concentration-dependent effect of the antibody on both aPTT and dRVVT prolongation was found. These observations suggest that LBPA is an important lipid target for aPl with potential functional implications for the immunopathogenesis of APS.
Sorice
M
M
Dipartimento di Medicina Sperimentale e Patologia, Università La Sapienza, Roma, Italy.
Ferro
D
D
Misasi
R
R
Pittoni
V
V
Longo
A
A
Circella
A
A
Garofalo
T
T
Gradini
R
R
Violi
F
F
Gruenberg
J
J
Valesini
G
G
D017152:Antibodies, Antiphospholipid / Q000276:immunology* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects*; D002451:Cell Compartmentation / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry; D004306:Dose-Response Relationship, Immunologic; D011992:Endosomes / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000276:immunology*; D018613:Microscopy, Confocal; D050178:Monoglycerides; D015388:Organelles / Q000737:chemistry; D010314:Partial Thromboplastin Time; D021381:Protein Transport; D011517:Prothrombin Time; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D008246:Lysophospholipids; D050178:Monoglycerides; D053482:beta 2-Glycoprotein I; C012786:bis(monoacylglyceryl)phosphate