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Pneumolysin Mediates Platelet Activation In Vitro

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Abstract

This study has explored the role of the pneumococcal toxin, pneumolysin (Ply), in activating human platelets. Following exposure to Ply (10–80 ng/ml), platelet activation and cytosolic Ca2+ concentrations were measured flow cytometrically according to the level of expression of CD62P (P-selectin) and spectrofluorimetrically, respectively. Exposure to Ply resulted in marked upregulation of expression of platelet CD62P, achieving statistical significance at concentrations of 40 ng/ml and higher (P < 0.05), in the setting of increased influx of Ca2+. These potentially pro-thrombotic actions of Ply were attenuated by depletion of Ca2+ from the extracellular medium or by exposure of the cells to a pneumolysoid devoid of pore-forming activity. These findings are consistent with a mechanism of Ply-mediated platelet activation involving sub-lytic pore formation, Ca2+ influx, and mobilization of CD62P-expressing α-granules, which, if operative in vivo, may contribute to the pathogenesis of associated acute lung and myocardial injury during invasive pneumococcal disease.

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Authors and Affiliations

  1. Department of Haematology, Faculty of Health Sciences, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, PO Box 2034, Pretoria, 0001, South Africa

    Jan Gert Nel

  2. Institute for Cellular and Molecular Medicine, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Chrisna Durandt & Ronald Anderson

  3. Department of Internal Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Gregory R. Tintinger

  4. Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    Timothy J. Mitchell

  5. Division of Pulmonology, Department of Internal Medicine, Faculty of Health Sciences, and Charlotte Maxeke Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa

    Charles Feldman

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  1. Jan Gert Nel
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  2. Chrisna Durandt
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  3. Timothy J. Mitchell
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  4. Charles Feldman
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  5. Ronald Anderson
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  6. Gregory R. Tintinger
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Correspondence to Jan Gert Nel.

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Nel, J.G., Durandt, C., Mitchell, T.J. et al. Pneumolysin Mediates Platelet Activation In Vitro. Lung 194, 589–593 (2016). https://doi.org/10.1007/s00408-016-9900-5

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  • DOI: https://doi.org/10.1007/s00408-016-9900-5

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