Platelet plug formation in whole blood is enhanced in the presence of Porphyromonas gingivalis

Abstract

Hemostasis involves a highly regulated equilibrium between pro and anticoagulant processes. It is a dynamic system comprising cellular and plasma factors that interact with damaged vascular tissue to minimize blood loss. Platelets are anucleate cellular fragments derived from mature megakaryocytes via a process called thrombopoiesis (Stegner et al., 2017). They circulate throughout the vascular system in a quiescent discoid form, interacting minimally with healthy endothelial cells. Following injury to the endothelium, platelets serve as key effector cells for the hemostatic response. They rapidly adhere to exposed extracellular matrix via tether receptor complexes such as collagen-glycoprotein (GP) VI and von Willebrand factor-GPIb-V-IX (Canobbio et al., 2004; Chen et al., 2002). Platelet attachment triggers downstream effects including the release of platelet-specific α granules and dense granules (Blair & Flaumenhaft, 2009; Li et al., 2010). Contained within these granules are important membrane bound receptors (GPIIb/IIIa and P-selectin), platelet mediators (adenosine 5ʹ-diphosphate [ADP] and calcium ions; Blair et al., 2009; Sharda & Flaumenhaft, 2018). Release of ADP, a potent platelet agonist, is crucial for the formation of an effective platelet plug. Such ADP mediated activation leads to morphological changes, transforming resting discoid platelets to an amoeboid state with numerous pseudopodia that facilitate platelet interdigitation and stabilize the developing aggregate

Platelet and neutrophil responses to Porphyromonas gingivalis in human whole blood

“…In the presence of added ADP, significant increases in labeled neutrophilassociated DNA were measured in whole blood preincubated with P. gingivalis (Dwass, Steel, Critchlow-Fligner, p < .05). *p < .05; n.s., not significant preincubation with lower P. gingivalis CFU can lead to a more pronounced platelet response (Chen et al, 2020). Bacterial interaction with platelets can induce aggregation via direct or indirect mechanisms that bind to surface platelet receptors, such as GPIb, GPIIb/IIIa, and TLRs (Hamzeh-Cognasse et al, 2015).…”

“…Thus, prolonging preincubation with lower P . gingivalis CFU can lead to a more pronounced platelet response (Chen et al., 2020).…”

“…No bacterial colonies were observed, indicating that P. gingivalis cells were not viable. Colony forming unit (CFU) calculations for HK suspensions and P. gingivalis cultures were based on the formula from previous W83 colony count assays used earlier (Chen et al, 2020):…”

“…Colony forming unit (CFU) calculations for HK suspensions and P . gingivalis cultures were based on the formula from previous W83 colony count assays used earlier (Chen et al., 2020):…”

Local and Systemic Effects of Porphyromonas gingivalis Infection

“…Similarly, agonist-dependent increases in platelet P-selectin expression are observed after systemic P. gingivalis infusion into rats [ 267 ]. Preincubation of P. gingivalis with whole blood also impacts platelet plug formation under shear conditions [ 268 ]. Extending P. gingivalis preincubation times past 7.5 min significantly reduces the time for platelet plug-mediated aperture occlusion in the Platelet Function Analyzer (PFA-100).…”