Cyclic-AMP Agonists Inhibit Antiphospholipid/ß₂-Glycoprotein I Induced Synthesis of Human Platelet Thromboxane A₂ in Vitro

REGINALD OPARA, DICK L. ROBBINS, and VINCENT A. ZIBOH

ABSTRACT.

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/ß₂-glycoprotein I (aCL/ß₂-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/ß₂-GPI induced platelet TXB₂ production in vitro. Isolated human platelets were prelabeled with ¹⁴C-arachidonic acid and then challenged with aCL/ß₂-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/ß₂-GPI induced platelet TXB₂ production by the cAMP agonists in a dose dependent manner.

Conclusion. Our findings suggest the usefulness of cAMP agonists in the control of thrombosis in some patients with SLE and APS. (J Rheumatol 2003;30:55-9)

Key Indexing Terms:

ANTIPHOSPHOLIPID ANTIBODIES
THROMBOXANE A₂
ANTIPHOSPHOLIPID SYNDROME
PLATELETS

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From the Department of Dermatology and Department of Internal Medicine, School of Medicine, University of California at Davis, Davis, California, USA.

R. Opara, BS, Medical Student; V.A. Ziboh, PhD, Professor of Dermatology, Department of Dermatology; D.L. Robbins, MD, Professor of Medicine, Department of Internal Medicine.

Address reprint requests to Dr. D.L. Robbins, Department of Internal Medicine, TB 192, School of Medicine, University of California at Davis, Davis, CA 95616. E-mail: dlrobbins@ucdavis.edu

Submitted May 18, 2001; revision accepted July 10, 2002.

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