Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells--inhibition of thrombomodulin-dependent protein C activation.
We have investigated the effect of purified immunoglobulin G (IgG) on endothelial cell functions in 16 patients with lupus anticoagulant, 9 of whom had systemic lupus erythematosus (SLE). Spontaneous or thrombin-stimulated secretion of prostacyclin (PGI2) by cultured human endothelial cells from umbilical cord vein (HUVEC) was not inhibited by the patient's IgG. Nor was spontaneous release of tissue plasminogen activator (t-PA) or of its inhibitor (PAI) modified in the presence of patient's IgG. The rate of activation of purified protein C (PC) by HUVEC in the presence of thrombin was significantly lowered by patient's IgG or Fab' fragment (inhibition of 43%). Neutralization of this effect was obtained by incubation of a greater quantity of phospholipids (phosphatidylcholine, phosphatidylserine) with the patient's IgG. Activation of PC was also performed using purified rabbit thrombomodulin (TM) and a similar inhibition of the patient IgG was observed (inhibition of 48%) but the activation of Gla-domainless PC was not modified.
Cariou
R
R
INSERM U 150, CNRS UA 334-Hôpital Lariboisière, Paris, France.
Tobelem
G
G
Bellucci
S
S
Soria
J
J
Soria
C
C
Maclouf
J
J
Caen
J
J
D000818:Animals; D001778:Blood Coagulation Disorders / Q000503:physiopathology*; D001779:Blood Coagulation Factors / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification; D016682:Lupus Coagulation Inhibitor; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors; D015849:Plasminogen Inactivators; D011486:Protein C / Q000502:physiology*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000502:physiology*; D018179:Receptors, Thrombin; D013917:Thrombin; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D001779:Blood Coagulation Factors; D006023:Glycoproteins; D007074:Immunoglobulin G; D016682:Lupus Coagulation Inhibitor; D015849:Plasminogen Inactivators; D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D011464:Epoprostenol; D010960:Plasminogen Activators; D013917:Thrombin; D010959:Tissue Plasminogen Activator