Adenosine Receptor Agonism Protects Against NETosis and Thrombosis in Antiphospholipid Syndrome

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Apr 25

PMID 31015489

Citations 103

Authors

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

Yogendra Kanthi

Jason S Knight

Affiliations

Soon will be listed here.

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 A 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 A 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.

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