Lupus anticoagulant antibodies inhibit collagen-induced adhesion and aggregation of human platelets in vitro.
The effect of circulating lupus anticoagulant on platelet interaction with collagen and other proteins was tested, with the aim of understanding the role of membrane phospholipids in platelet function. Plasma samples from 26 systemic lupus erythematosus (SLE) patients, containing circulating lupus anticoagulant (LAC), were examined for their effect on adhesion and aggregation of normal human platelets. We find that SLE plasma, but not normal plasma, inhibits platelet adhesion to collagen in a concentration-dependent manner. At a plasma concentration of 1% the inhibition was 73 +/- 9% (mean +/- SD). In sharp contrast, there was no effect on platelet adhesion to fibronectin. Purified IgG from the same plasma samples also had an inhibitory effect. At 15 micrograms/ml (comparable in IgG concentration to 0.1% plasma) it inhibited adhesion to collagen by 33 +/- 11%. Inhibition could be abolished by preincubation of the LAC-containing plasma with cardiolipin (CL), phosphatidylinositol (PI), and, to a lesser extent, phosphatidylserine (PS) but not with phosphatidylcholine (PC) or phosphatidylethanolamine (PE). Inhibition could also be abolished by preincubation of the LAC-containing plasma with a 10-fold excess of washed normal platelets. The effect of 1% LAC plasma on platelet aggregation was as striking, showing 79 +/- 26% inhibition of collagen-induced aggregation, and it could also be abolished by preincubation of the LAC plasma with cardiolipin. In contrast, the effect of LAC plasma on thrombin-induced aggregation was rather modest. Our results indicate that antiphospholipid antibodies interfere with platelet adhesion and stimulation by collagen in vitro and point to an important role of external plasma membrane phospholipids, particularly PI, in collagen-induced platelet activation.
Ostfeld
I
I
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Dadosh-Goffer
N
N
Borokowski
S
S
Talmon
J
J
Mani
A
A
Zor
U
U
Lahav
J
J
D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D003094:Collagen / Q000276:immunology*; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D010973:Platelet Adhesiveness / Q000276:immunology*; D010974:Platelet Aggregation / Q000276:immunology*; D010975:Platelet Aggregation Inhibitors / Q000276:immunology; D013928:Thromboxane A2 / Q000096:biosynthesis
D001323:Autoantibodies; D005353:Fibronectins; D016682:Lupus Coagulation Inhibitor; D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D003094:Collagen