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Platelet Activation Is Induced via Myeloperoxidase Production and Anti-Myeloperoxidase Antibodies Primed by Thrombin
32 Pages Posted: 11 Jun 2019
More...Abstract
In addition to their central role in hemostasis and thrombosis, platelets involve in inflammatory responses. Anti-neutrophil cytoplasmic autoantibodies (ANCAs) directed to myeloperoxidase (MPO-ANCAs) are the main serological markers of ANCA-associated vasculitis. The current study demonstrated that MPO-ANCAs caused normal human platelets to activate, primed by low doses of thrombin. Purified immunoglobulin G, MPO-ANCAs and their F(ab')2 fragments evidently increased the CD62P expression of platelets compared with controls. The existence of MPO in platelets was confirmed with mass spectrometry technology, after analyzing the F(ab')2 fragment pull-downed proteins. After thrombin priming, platelets not only expressed MPO on the surface with an activation-dependent manner, but also released the enzyme to extracellular space. These effects markedly enhanced the activation of platelets. Additionally, there was no apparently increased CD62P-expression on platelets in MPO-ANCAs group compared with controls when adding MPO inhibitor, proving that primed platelets have ANCA antigen at their surfaces interacting with the autoantibodies. These findings suggest a previously unappreciated character for platelets as immune cells and the autoantibodies-induced activation in an acute inflammatory disease.
Funding: This study was supported by the grant from the National Key Research and Development Program (No. 2016YFC0906102), three grants from the National Natural Science Fundation of China (No. 81870478, 81425008 and 81621092) and the grant of University of Michigan Health System and Peking University Health Sciences Center Joint Institute for Translational and Clinical Research, and Program of Changjiang Scholar (BMU2017CJ002).
Declaration of Interest: All the authors declared no competing interests.
Ethical Approval: The study was in compliance with the Declaration of Helsinki and was approved by the ethics committees of Peking University First Hospital.
Keywords: platelets, myeloperoxidase, autoantibody, ANCA, vasculitis
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