Desialylation of Platelets by Pneumococcal Neuraminidase A Induces ADP-Dependent Platelet Hyperreactivity.

Autor:	Kullaya V; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands vesla.kullaya@radboudumc.nl.; Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.; Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania., de Jonge MI; Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.; Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands., Langereis JD; Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.; Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands., van der Gaast-de Jongh CE; Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.; Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands., Büll C; Department of Radiation Oncology, Radiotherapy and Oncoimmunology Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands., Adema GJ; Department of Radiation Oncology, Radiotherapy and Oncoimmunology Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands., Lefeber D; Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands., Cremers AJ; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Mmbaga BT; Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania., de Groot PG; Department of Clinical Chemistry and Haematology, University Medical Centre, Utrecht, The Netherlands., de Mast Q; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands., van der Ven AJ; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2018 Sep 21; Vol. 86 (10). Date of Electronic Publication: 2018 Sep 21 (Print Publication: 2018).
DOI:	10.1128/IAI.00213-18
Abstrakt:	Platelets are increasingly recognized to play a role in the complications of Streptococcus pneumoniae infections. S. pneumoniae 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 ex vivo 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. (Copyright © 2018 American Society for Microbiology.)
Databáze:	MEDLINE
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