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Adenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome

Author

Listed:
  • Ramadan A. Ali

    (University of Michigan)

  • Alex A. Gandhi

    (University of Michigan)

  • He Meng

    (University of Michigan)

  • Srilakshmi Yalavarthi

    (University of Michigan)

  • Andrew P. Vreede

    (University of Michigan)

  • Shanea K. Estes

    (University of Michigan)

  • Olivia R. Palmer

    (University of Michigan)

  • Paula L. Bockenstedt

    (University of Michigan Medical School)

  • David J. Pinsky

    (University of Michigan
    University of Michigan)

  • Joan M. Greve

    (University of Michigan)

  • Jose A. Diaz

    (University of Michigan)

  • Yogendra Kanthi

    (University of Michigan
    Ann Arbor Veterans Administration Healthcare System)

  • Jason S. Knight

    (University of Michigan)

Abstract

Potentiation of neutrophil extracellular trap (NET) release is one mechanism by which antiphospholipid antibodies (aPL Abs) effect thrombotic events in patients with antiphospholipid syndrome (APS). Surface adenosine receptors trigger cyclic AMP (cAMP) formation in neutrophils, and this mechanism has been proposed to regulate NETosis in some contexts. Here we report that selective agonism of the adenosine A2A receptor (CGS21680) suppresses aPL Ab-mediated NETosis in protein kinase A-dependent fashion. CGS21680 also reduces thrombosis in the inferior vena cavae of both control mice and mice administered aPL Abs. The antithrombotic medication dipyridamole is known to potentiate adenosine signaling by increasing extracellular concentrations of adenosine and interfering with the breakdown of cAMP. Like CGS21680, dipyridamole suppresses aPL Ab-mediated NETosis via the adenosine A2A receptor and mitigates venous thrombosis in mice. In summary, these data suggest an anti-inflammatory therapeutic paradigm in APS, which may extend to thrombotic disease in the general population.

Suggested Citation

  • Ramadan A. Ali & Alex A. Gandhi & He Meng & Srilakshmi Yalavarthi & Andrew P. Vreede & Shanea K. Estes & Olivia R. Palmer & Paula L. Bockenstedt & David J. Pinsky & Joan M. Greve & Jose A. Diaz & Yoge, 2019. "Adenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09801-x
    DOI: 10.1038/s41467-019-09801-x
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