[Show abstract][Hide abstract] ABSTRACT: 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.
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 alphaIIbbeta3 integrin and glycoprotein Ib, each inhibited the secretion of all factors.
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.
[Show abstract][Hide abstract] ABSTRACT: Blood platelets link the processes of haemostasis and inflammation. This study examined the immunomodulatory factors released by platelets after Toll-Like Receptor 4 (TLR4) engagement on their surfaces. Monoclonal anti-human FcgammaRII Ab (IV.3)-treated human platelets were cultured with TLR4 ligands in the presence or absence of blocking monoclonal antibody to human TLR4. The release of sCD62p, epidermal growth factor (EGF), transforming growth factor beta (TGFbeta), interleukin (IL)-8, platelet activating factor 4 (PAF4), platelet-derived growth factor, alpha, beta polypeptide (PDGF-AB), Angiogenin, RANTES (regulated upon activation, normal T-cell expressed, and presumably secreted) and sCD40L were measured by specific enzyme-linked immunosorbent assay. TLR4 ligand [Escherichia coli lipopolysaccharide (LPS)] bound platelet TLR4, which differentially modulates the release of cytokines by platelets. It was noted that (i) sCD62p, IL-8, EGF and TGFbeta release were each independent of platelet activation after TLR4 engagement; (ii) RANTES, Angiogenin and PDGF-AB concentration were weaker in platelet supernatant after TLR4 engagement; (iii) sCD40L and PAF4 are present in large concentration in the releaseate of platelets stimulated by TLR4 ligand. The effects of LPS from E. coli on the modulation of secretory factors were attenuated by preincubation of platelets with an anti-TLR4 monoclonal antibody, consistent with the immunomodulation being specifically mediated by the TLR4 receptor. We propose that platelets adapt the subsequent responses, with polarized cytokine secretion, after TLR4 involvement.
British Journal of Haematology 05/2008; 141(1):84-91. · 4.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemostasis is a finely balanced process in which an insult to a blood vessel wall, either by injury or surgical intervention, stimulates a pair of parallel, yet associated, pathways that lead to the termination of blood loss. The coagulation cascade is initiated by the interaction between exposed subendothelial tissue factor and circulating blood and includes a series of amplification steps that result in thrombin generation. Concurrently, exposed subendothelial collagen stimulates platelets, which, in the presence of thrombin, are consolidated by fibrin to form a blood clot, thus terminating blood loss. Multiple inherited and acquired abnormalities in these pathways can seriously compromise hemostasis. Furthermore, several drugs, including over-the-counter preparations, also adversely affect hemostasis. These present significant concerns to the dentist conducting invasive procedures as they can prolong postoperative bleeding, impair wound healing and increase risk of infection. In this article, we review the current knowledge of bleeding abnormalities and discuss preoperative systemic precautions and intraoperative hemostatic measures.