Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Infect Immun. 2018 Sep 21;86(10). doi: 10.1128/IAI.00213-18. Print 2018 Oct.
Platelets are increasingly recognized to play a role in the complications of infections. expresses neuraminidases, which may alter glycans on the platelet surface. In the present study, we investigated the capability of pneumococcal neuraminidase A (NanA) to remove sialic acid (desialylation) from the platelet surface, the consequences for the platelet activation status and reactivity, and the ability of neuraminidase inhibitors to prevent these effects. Our results show that soluble NanA induces platelet desialylation. Whereas desialylation itself did not induce platelet activation (P-selectin expression and platelet fibrinogen binding), platelets became hyperreactive to stimulation by ADP and cross-linked collagen-related peptide (CRP-XL). Platelet aggregation with leukocytes also increased. These processes were dependent on the ADP pathway, as inhibitors of the pathway (apyrase and ticagrelor) abrogated platelet hyperreactivity. Inhibition of NanA-induced platelet desialylation by neuraminidase inhibitors (e.g., oseltamivir acid) also prevented the platelet effects of NanA. Collectively, our findings show that soluble NanA can desialylate platelets, leading to platelet hyperreactivity, which can be prevented by neuraminidase inhibitors.
血小板在感染并发症中扮演着越来越重要的角色。肺炎链球菌表达神经氨酸酶，这可能会改变血小板表面的聚糖。在本研究中，我们研究了肺炎链球菌神经氨酸酶 A (NanA) 将唾液酸（去唾液酸化）从血小板表面去除的能力、对血小板激活状态和反应性的影响，以及神经氨酸酶抑制剂预防这些作用的能力。我们的结果表明，可溶性 NanA 可诱导血小板去唾液酸化。然而，去唾液酸化本身并不会诱导血小板激活（P-选择素表达和血小板纤维蛋白原结合），但会使血小板对 ADP 和交联胶原相关肽（CRP-XL）的刺激更加敏感。血小板与白细胞的聚集也增加了。这些过程依赖于 ADP 途径，因为该途径的抑制剂（apyrase 和 ticagrelor）可消除血小板的高反应性。神经氨酸酶抑制剂（如奥司他韦酸）抑制 NanA 诱导的血小板去唾液酸化也能预防 NanA 对血小板的作用。总之，我们的研究结果表明，可溶性 NanA 可以使血小板去唾液酸化，导致血小板高反应性，而神经氨酸酶抑制剂可以预防这种反应。
