title: The Dynamics of Platelet Activation during the Progression of Streptococcal Sepsis.
abstract: Platelets contribute to inflammation however, the role of platelet activation during the pathophysiological response to invasive bacterial infection and sepsis is not clear. Herein, we have investigated platelet activation in a mouse model of invasive Streptococcus pyogenes infection at 5, 12, and 18 hours post infection and correlated this to parameters of infection. The platelet population in ex-vivo blood samples showed no increased integrin activation or surface presentation of CD62P, however platelet-neutrophil complex formation and plasma levels of CD62P were increased during bacterial dissemination and the progression of sepsis, indicating that platelet activation had occurred in vivo. Platelet-neutrophil complex formation was the most discriminatory marker of platelet activation. Platelet-neutrophil complexes were increased above baseline levels during early sepsis but decreased to significantly lower levels than baseline during late sepsis. The removal of these complexes from the circulation coincided with a significant increase in organ damage and the accumulation of platelets in the liver sinusoids, suggesting that platelet activation in the circulation precedes accumulation of platelets in damaged organs. The results demonstrate that monitoring platelet activation using complementary methods may provide prognostic information during the pathogenesis of invasive S. pyogenes infection.
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, SE- 22184 Lund, Sweden.
authors.forename: Sinead M
authors.initials: SM
authors.lastname: Hurley
authors.affiliation: Imagene-iT AB, Medicon Village, SE22381 Lund, Sweden.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Lutay
authors.affiliation: Imagene-iT AB, Medicon Village, SE22381 Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Holmqvist
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, SE- 22184 Lund, Sweden.
authors.forename: Oonagh
authors.initials: O
authors.lastname: Shannon