Isolation and purification of anticardiolipin antibody from plasma of a patient with antiphospholipid syndrome: induced generation of platelet thromboxane A2 synthesis.
Antiphospholipid antibodies, particularly anticardiolipin antibodies (aCL) are autoantibodies frequently detected in the serum of patients with systemic lupus erythematosus (SLE) and the primary antiphospholipid antibody syndrome (PAPS). These patients commonly suffer from thrombosis, recurrent fetal loss and thrombocytopenia. Since platelet aggregation is pivotal in the genesis of thrombosis, we tested the hypothesis that perturbation of platelet membrane by aCL/beta 2-glycoprotein (aCL/beta 2GP) complex could trigger the biosynthesis of TXA2, a proaggregatory metabolite of AA. The preincubation of 14C-arachidonic acid (14C-AA)-labeled platelet pellets (14C-PP) from normal individuals with aCL alone followed by incubation with thrombin, resulted in a moderate increase in platelet thromboxane B2 (14C-TXB2) biosynthesis when compared to controls (without aCL). Similar incubations with beta 2GP-I alone resulted in negligible 14C-TXB2 biosynthesis. In contrast, the preincubations of normal 14C-PP with aCL/beta 2GP-I complex resulted in marked thrombin-induced TXB2 biosynthesis, underscoring the requirement of beta 2GP-I in aCL-induced platelet TXB2 biosynthesis. Taken together, these results are consistent with the view that aCL/beta 2GP-I platelet interactions do play a role, at least in part, in platelet hyperactivity and thrombosis in antiphospholipid antibody syndrome.
Leung
S
S
Department of Dermatology, University of California, School of Medicine, Davis 95616, USA.
Ziboh
V A
VA
Miller-Blair
D J
DJ
Robbins
D L
DL
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood* / Q000302:isolation & purification* / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001011:Aorta / Q000473:pathology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002846:Chromatography, Affinity / Q000379:methods; D002852:Chromatography, Ion Exchange / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000150:complications / Q000276:immunology; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; C029152:G-substrate; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D053482:beta 2-Glycoprotein I; D013929:Thromboxane B2; D013928:Thromboxane A2; D013917:Thrombin