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Mcnicol A.,University of Manitoba | Agpalza A.,University of Manitoba | Jackson E.C.G.,University of Manitoba | Hamzeh-Cognasse H.,Etablissement Francais du Sang EFS Auvergne Loire | And 5 more authors.
Journal of Thrombosis and Haemostasis | Year: 2011

Background: There is increasing evidence that both chronic and acute infections play a role in the development and progression of atherothrombotic disorders. One potential mechanism is the direct activation of platelets by bacteria. A wide range of bacterial species activate platelets through heterogeneous mechanisms. The oral micro-organism S. sanguinis stimulates platelet aggregation in vitro in a strain-dependent manner, although there are no reports of associated cytokine production. Objective: The aim of the present study was to determine whether platelet activation by S. sanguinis involved the release of pro-inflammatory and immune modulating factors, and whether activation was enhanced by epinephrine. Methods and results: Four strains of S. sanguinis and one of S. gordonii stimulated the release of RANTES, PF4, sCD40L and PDGF-AB, whereas only one S. sanguinis strain caused the release of sCD62p. Epinephrine enhanced S. sanguinis-induced platelet aggregation and phosphorylation of phospholipase Cγ2 and Erk, but inhibited RANTES, PF4, sCD40L and PDGF-AB release. Wortmannin inhibited S. sanguinis-induced aggregation and release; however, only aggregation was partially reversed by epinephrine. Conclusions: The present study demonstrates that platelets respond to S. sanguinis with both prothrombotic and pro-inflammatory/immune-modulating responses. Epinephrine, potentially released in response to infection and/or stress, can significantly enhance the prothrombotic response, thereby providing a putative link between bacteraemia and acute coronary events during stress. In contrast, epinephrine inhibited the pro-inflammatory/immune-modulating response by an undetermined mechanism. © 2011 International Society on Thrombosis and Haemostasis.


PubMed | Etablissement Francais du Sang EFS Auvergne Loire, U.S. National Institutes of Health and Jean Monnet University
Type: | Journal: BMC immunology | Year: 2015

The concept of the immunogenicity of an antigen is frequently encountered in the context of vaccine development, an area of intense interest currently due to the emergence or re-emergence of infectious pathogens with the potential for worldwide spread. However, the theoretical notion of immunogenicity as discussed in older textbooks of immunology needs reconsideration due to advances in our understanding of immunologic responses. Immunogenicity is a property that can either be a desirable attribute, for example in the generation of an effective protective immunity against infectious pathogens or an undesirable trait, for example when it relates to novel therapeutic compounds and drugs, where an immune response needs to be prevented or inhibited. In this Forum Article, we aimed to revisit the issue of immunogenicity to discuss a series of simple questions relevant to the concept that are frequently rephrased but incompletely resolved in the immunologic literature.


PubMed | Etablissement Francais du Sang EFS Auvergne Loire
Type: | Journal: BMC immunology | Year: 2014

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 IIb3 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.

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