Streptococcus sanguinis-induced cytokine and matrix metalloproteinase-1 release from platelets

Background: Streptococcus sanguinis (S. sanguinis), a predominant bacterium in the human oral cavity, has been widely associated with the development of infective endocarditis. Platelets play both a haemostatic function and can influence both innate and adaptive immune responses. Previous studies have shown that S. sanguinis can interact with, and activate, platelets. Results: The aim of this study was to determine whether S. sanguinis stimulates the release of matrix metalloproteinases (MMPs) 1, 2 and 9 and the pro-inflammatory mediators SDF-1, VEGF and sCD40L, from platelets and to subsequently pharmacologically address the release mechanism (s). S. sanguinis stimulated the release of MMP-1, SDF-1, VEGF and sCD40L from platelets and inhibitors of cyclooxygenase and phosphatidylinositol 3-kinase, and antagonists of the alpha IIb beta 3 integrin and glycoprotein Ib, each inhibited the secretion of all factors. Conclusions: Therefore the release of MMP-1, SDF-1, VEGF and sCD40L occurs late in the platelet response to S. sanguinis and highlights the complex intracellular signalling pathways stimulated in response to S. sanguinis which lead to haemostasis, MMP and pro-inflammatory mediator secretion.