Abstract:
This study has explored the role of the pneumococcal toxin, pneumolysin (Ply), in
activating human platelets. Following exposure to Ply [10–80 nanograms (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 Plymediated
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.
