Abstract Number: PB0722
Meeting: ISTH 2020 Congress
Background: Plasma factor XIII consists of two potentially active A subunits (FXIII-A) and two carrier/inhibitory B subunits. Its cellular form (cFXIII), a dimer of FXIII-A, is present in platelets in high concentration. cFXIII is of cytoplasmic localization, not released by the usual secretion mechanisms. It is present in microparticles (MPs), sub-micron seize extracellular vesicles, shed from cells upon activation by strong stimuli. Platelets activated by convulxin (CVX) and thrombin externalize cFXIII (Mitchell et al. Blood 2014;124:3982-90) and also induce the transposition of phosphatidylserine (PS) to the surface of activated platelets.
Aims: Monitoring the surface exposure of FXIII-A and PS on platelets undergoing receptor-, and non-receptor mediated activation and on the formed microparticles.
Methods: To generate MPs, gel-filtered platelets were stimulated by CVX, thrombin, CVX+thrombin or Ca2+-ionophore (A23187). Platelets and platelet derived MPs were identified by anti CD41a antibodies. For flow cytometry monoclonal FITC-labeled anti-human FXIII-A antibody and phycoerythrin-conjugated annexin V were used. In immunfluorescent studies FXIII-A was labeled by rabbit polyclonal anti-human FXIII-A and DyLight 488-labeled horse anti-rabbit IgG, annexin V was conjugated to Alexa Fluor 568. Platelets and MPs were incubated with the labeled antibodies, then analyzed by flow cytometry and by immunfluorescent microscopy.
Results: After receptor-mediated activation of platelets with CVX+thrombin 35% of platelets and more than half of MPs became annexin V-positive and cFXIII-A became transposed to the outer membrane surface in 66% of platelets and 65% of MPs. The overwhelming majority of PS-positive platelets and MPs also showed FXIII-A positivity. Non-receptor mediated activation triggered by Ca2+-ionophore resulted annexin V positive platelets and MPs, however neither the cells nor the formed MPs expressed FXIII-A on their surface.
Conclusions: Receptor-mediated platelet activation induced the transposition of FXIII-A to the surface of activated cells and the formed microparticles, while non-receptor mediated activation failed to externalize cFXIII.
To cite this abstract in AMA style:Somodi L, Beke Debreceni I, Bárdos H, Bana Á, Kappelmayer J, Muszbek L. Cellular Factor XIII Externalization in Platelets and Platelet Microparticles Induced by Receptor Mediated and Non-Receptor Mediated Platelet Activation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/cellular-factor-xiii-externalization-in-platelets-and-platelet-microparticles-induced-by-receptor-mediated-and-non-receptor-mediated-platelet-activation/. Accessed May 6, 2021.
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