Abstract Number: PB0109
Meeting: ISTH 2021 Congress
Theme: Coagulation and Natural Anticoagulants » Microparticles
Background: We previously reported that porphyromonas gingivalis (P.gingivalis), a periodontal pathogen, activates HUVEC endothelial cells and the shedding of microvesicles (MVs) that act as autocrine pro-inflammatory and apoptotic effectors [Bugueno et al., Sci Rep. 2020;10(1):1778].
Aims: To assess the effects of mechanical jaw injury, eventually combined to local P.gingivalis infection, and of intraperitoneal P.gingivalis infection alone on the spleen response in a C57BL 6 murine model of periondontitis.
Methods: A 2-weeks jaw injury was performed by silk (LIG) or P.gingivalis soaked ligatures (LIG-PG) and compared to P.gingivalis intraperitoneal injection (IP). Inhibition of Netosis was performed in IP-treated mice by simultaneous injection of Cl-amidine, a PAD4-4 inhibitor. Spleen MVs (SMVs) were extracted and characterized by protein and prothrombinase assays, and their diameter measured by TRPS. Cellular composition of the spleen was determined by flow cytometry, reactive oxygen species (ROS) measured on sections by DHE fluorescent probing, markers of inflammation and activation by western blot.
Results: In spleen-treated mice, a 2-fold spleen weight was associated with elevated SMV concentration (IP: 210±38, LIG-PG:175±5, LIG:150±4 vs. CTL:100±6 nM PhtdSer eq., p<0.05) having a 188-200 nm diameter range. ROS accumulation followed the same pattern (IP: 77,27±0.5, LIG-PG: 59,5±13, LIG: 31±12, CTL:6,7 ±1,3, A.U./p<0.05). In LIG and LIG-PG, tissue factor and VCAM expression was doubled. In IP-treated mice, spleen neutrophils (15% vs 0.1% ), granulocytes (10% vs. 0.5%) and monocytes (4.5% vs 0.5%) increased drastically while T4, T8 and B lymphocytes were reduced by half (p<0.05). Cl-amidine inhibited 79% of IP-induced ROS accumulation, pointing at Netosis contribution.
Conclusions: Data suggest that P.gingivalis-associated periodontitis induces remote spleen activation, Netosis and the shedding of procoagulant SMVs. Measurement of plasma Nets fragments and further characterization of SMV effects on coronary endothelial cells are needed to decipher the link between cardiovascular risk and periodontitis.
To cite this abstract in AMA style:
EL Itawi H, Amissi S, Batool F, Stutz C, El Ghazouani F, Chaker AB, Qureshi AW, Moschovaki-Filippidou F, Auger C, Anglès-Cano E, Huck O, Toti F. Peridontal Injury Prompts Remote Spleen Activation and the Generation of Spleen Procoagulant Microvesicles in a Periodontitis Murine Model [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/peridontal-injury-prompts-remote-spleen-activation-and-the-generation-of-spleen-procoagulant-microvesicles-in-a-periodontitis-murine-model/. Accessed November 30, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/peridontal-injury-prompts-remote-spleen-activation-and-the-generation-of-spleen-procoagulant-microvesicles-in-a-periodontitis-murine-model/