Bacteria-induced intracellular signalling in platelets. (June 2015)

• Record Type: Journal Article
• Authors: McNicol, Archie
• Is Part Of: Platelets. Volume 26:Number 4(2015:Jun.)
• Page Start: 309
• Page End: 316
• Publication Date: 2015-06
• Subjects: Blood platelets -- Periodicals; Blood Platelets -- Periodicals; 615.39
• DOI: 10.3109/09537104.2015.1014470
• Languages: English
• ISSNs: 0953-7104

Abstract

<abstract> <title>Abstract</title> <p>Multiple studies have now shown that various species of bacteria can stimulate platelets; many in a strain and donor-dependent manner. The signalling pathways underlying this platelet activation has been the subject of scrutiny for the last decade. The best-delineated pathway is that in response to <italic>Streptococcal</italic> species, such as <italic>Streptococcus sanguinis</italic> (<italic>S. sanguinis</italic>), <italic>Streptococcus gordonii</italic> (<italic>S. gordonii</italic>) and <italic>Streptococcus oralis</italic> (<italic>S. oralis</italic>), where a pathway is initiated by the engagement of the low affinity IgG receptor, FcγRIIA. This leads to and involves the tyrosine kinase Syk, the adaptor protein Linker of Activated T Cells (LAT) and subsequently both phospholipase Cγ2 (PLCγ2) and phosphatidylinositol-3-kinase (PI-3-K). Finally, this leads to the expression of the αIIbβ3 integrin, the synthesis and release of thromboxane A<sub>2</sub> (T × A<sub>2</sub>) and the exocytosis of PF4, each of which plays a crucial role in secondary signalling and full platelet activation. Roles for other signalling pathways in <italic>Streptococcal</italic>-induced platelet activation are less clear, although an ADP-mediated inhibition of adenylyl cyclase, a glycoprotein Ib/IX/V-mediated pathway and perhaps a complement-induced pathway have each been proposed. Platelet activation by <italic>Porphyromonas gingivalis</italic> (<italic>P. gingivalis</italic>) at least partially shares the FcγRIIA/Syk/PLCγ2/PI-3-K mechanism utilised by <italic>Streptococcal</italic> species. However, it has also been suggested that <italic>P. gingivalis</italic> activates platelets by two additional methods; stimulation of the protease-activated receptors leading to activation of phospholipase Cβ (PLCβ), and the engagement of Toll-like receptors 2 and 4 by released lipopolysaccharide leading to an ill-defined pathway which may involve PI-3-K. Consequently, it appears that bacteria can stimulate platelets by eliciting multiple signalling pathways some of which are common, and some unique, to individual species.</p> </abstract>