Archie McNicol

University of Manitoba, Winnipeg, Manitoba, Canada

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Publications (4)10.53 Total impact

  • Archie McNicol
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    ABSTRACT: 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 Streptococcal species, such as Streptococcus sanguinis (S. sanguinis), Streptococcus gordonii (S. gordonii) and Streptococcus oralis (S. oralis), 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 A2 (T × A2) 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 Streptococcal-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 Porphyromonas gingivalis (P. gingivalis) at least partially shares the FcγRIIA/Syk/PLCγ2/PI-3-K mechanism utilised by Streptococcal species. However, it has also been suggested that P. gingivalis 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.
    No preview · Article · Mar 2015 · Platelets
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    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.
    Full-text · Article · Apr 2014 · BMC Immunology
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    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.
    Full-text · Article · May 2008 · British Journal of Haematology
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    Sara Israels · Nora Schwetz · Ron Boyar · Archie McNicol
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    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.
    Preview · Article · Dec 2006 · Journal (Canadian Dental Association)

Publication Stats

109 Citations
10.53 Total Impact Points


  • 2008-2015
    • University of Manitoba
      • • Department of Pharmacology and Therapeutics
      • • Department of Oral Biology
      Winnipeg, Manitoba, Canada