Cyclic-AMP agonists inhibit antiphospholipid/beta2-glycoprotein I induced synthesis of human platelet thromboxane A2 in vitro.
OBJECTIVE
To investigate mechanisms responsible for increased thrombotic activity in systemic lupus erythematosus (SLE) associated with the antiphospholipid syndrome (APS). We had reported that anticardiolipin/beta2-glycoprotein I (aCL/beta2-GPI) complexes induce platelet overactivity resulting in excessive production of thromboxane A2 (TXA2). Presumably this occurs by decreased platelet cyclic AMP (cAMP) activity and results in increased platelet aggregation.


METHODS
We stimulated platelet intracellular cAMP generation with known cAMP agonists (dibutyryl cAMP, theophylline, and prostaglandin E1) and measured aCL/beta2-GPI induced platelet TXB2 production in vitro. Isolated human platelets were prelabeled with 14C-arachidonic acid and then challenged with aCL/beta2-GPI in the presence or absence of cAMP-activating substances. The resulting 14C labeled TXB2 was quantified by thin layer chromatography and radioactive scanning.


RESULTS
We found a marked decrease in aCL/beta2-GPI induced platelet TXB2 production by the cAMP agonists in a dose dependent manner.


CONCLUSIONS
Our findings suggest the usefulness of cAMP agonists in the control of thrombosis in some patients with SLE and APS.
Opara
Reginald
R
Department of Dermatology, School of Medicine, University of California at Davis, 95616, USA.
Robbins
Dick L
DL
Ziboh
Vincent A
VA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017153:Antibodies, Anticardiolipin / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism*; D016718:Arachidonic Acid / Q000493:pharmacokinetics; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D000242:Cyclic AMP / Q000819:agonists* / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis*; D053482:beta 2-Glycoprotein I
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017153:Antibodies, Anticardiolipin; D002250:Carbon Radioisotopes; D006023:Glycoproteins; D006490:Hemostatics; D053482:beta 2-Glycoprotein I; D016718:Arachidonic Acid; D013928:Thromboxane A2; D000242:Cyclic AMP; D013917:Thrombin; D007213:Indomethacin