Background: In this study, we investigated the mechanism of platelet activation in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), as well as the activation of the alternative complement pathway by platelets in AAV. Methods: CD62P and platelet-leukocyte aggregates in AAV patients were tested by flow cytometry. Platelets were stimulated by plasma from active AAV patients. The effect of the thrombin-protease-activated receptors (PARs) pathway was evaluated by blocking thrombin or PAR1 antagonists. After platelets were activated by plasma from AAV patients, Ca/Mg-Tyrode's buffer and Mg-EGTA buffer were used to measure complement activation in liquid phase and on the surface of platelets. Results: The levels of CD62P-expressing platelets and platelet-leukocyte aggregates were significantly higher in active AAV patients than those in remission and normal controls. Platelets were activated by plasma from active AAV patients (percentage of CD62P-expressing platelets, 97.7±3% vs. 1±0.2%, p<0.0001, compared with those incubated with healthy donor plasma), and this was inhibited by thrombin or PAR1 antagonists (percentage of CD62P-expressing platelets, 97.7±3% vs. 2.7±1%, p<0.0001, 97.7±3% vs. 5±1.4%, p<0.0001, respectively). Platelets activated by plasma from AAV patients could trigger complement activation via the alternative pathway, as demonstrated by significant elevation of C3a, C5a, and sC5b-9 and significantly more C3c and C5b-9 deposition on the surface of platelets. Conclusions: Platelets were activated in AAV patients, and such activation was at least partially attributed to the thrombin-PARs pathway. Activated platelets triggered the alternative complement pathway in AAV.
CITATION STYLE
Miao, D., Li, D. Y., Chen, M., & Zhao, M. H. (2017). Platelets are activated in ANCA-associated vasculitis via thrombin-PARs pathway and can activate the alternative complement pathway. Arthritis Research and Therapy, 19(1). https://doi.org/10.1186/s13075-017-1458-y
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