Autoantibodies to kininogen-phosphatidylethanolamine complexes augment thrombin-induced platelet aggregation.
Autoantibodies to the zwitterionic phospholipid (PL), phosphatidylethanolamine (PE), have been described in patients with thrombotic disease. We have reported that certain anti-PE antibodies (aPE) are not specific for PE, but are directed to PE-binding plasma proteins, high molecular weight kininogen (HK) and low molecular weight kininogen (LK). Kininogens bind to platelets and inhibit thrombin-induced platelet aggregation. This inhibition is specific for thrombin because kininogens do not inhibit platelet aggregation induced by adenosine diphosphate (ADP), collagen or calcium ionophore. To date, a platelet kininogen receptor has not been described. We recently reported that purified kininogens bind to purified PE in vitro. This opens the possibility that kininogens can bind to platelets by virtue of exposed PE in the platelet membrane. We thus questioned if aPE can recognize platelet bound kininogens and negate their antithrombotic property. Our experiments support this possibility by demonstrating that exogenously added kininogen-dependent IgG aPE markedly increased thrombin-induced platelet aggregation in vitro but did not alter ADP-induced aggregation. In contrast, kininogen independent IgG aPE which recognized PE per se did not augment thrombin-induced platelet aggregation. These data support a hypothesis that kininogen dependent aPE may cause thrombosis in vivo due to disruption of the normal antithrombotic effects of kininogen.
Tokai University School of Medicine, Kanagawa, Japan.
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T
Sugi
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JA
McIntyre
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology*; D002417:Cattle; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D007704:Kininogens / Q000276:immunology*; D010714:Phosphatidylethanolamines / Q000276:immunology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000276:immunology*; D013917:Thrombin / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D007704:Kininogens; D010714:Phosphatidylethanolamines; D013917:Thrombin