Abstract Number: OC 29.2
Meeting: ISTH 2022 Congress
Background: Platelets contain a high amount of potentially active A subunit dimer of coagulation factor XIII (cellular FXIII; cFXIII). It is of cytoplasmic localization, not secreted, but becomes translocated to the surface of platelets activated by convulxin and thrombin (CVX+Thr) (Mitchell et al. Blood 2014;124:3982-90).
Aims: To explore the difference in cFXIII translocation on platelets and platelet microparticles between receptor mediated and non-receptor mediated platelet activation and how the translocation is related to cytoplasmic Ca2+ concentration. A further aim was to shed some light on the mechanism of cFXIII translocation.
Methods: Gel-filtered platelets were activated by CVX+Thr or Ca2+-ionophore (calcimycin). The translocation of cFXIII and phosphatidylserine (PS) to the surface of activated platelets and platelet-derived microparticles was investigated by flow cytometry, immunofluorescence and immune electron microscopy. Fluo-4-AM fluorescence was used for the measurement of intracellular Ca2+ concentration. The role of RhoA and the activation of cFXIII were tested by studying the effect of their inhibitors.
Results: Receptor mediated activation by CVX+Thr exposed cFXIII and PS to the surface of over 60% and 30% of platelets, respectively. Electron microscopy revealed microparticles with preserved membrane structure and also microparticles devoid of labeling for membrane glycoprotein CD41a. cFXIII was observed on both types of microparticles but was more abundant in the absence of CD41a. cFXIII translocation was eliminated by Rhosin, a RhoA inhibitor, while only partial decrease could be achieved by T101, a transglutaminase inhibitor. Non-receptor mediated activation of platelets by calcimycin highly elevated cytoplasmic Ca2+ concentration, it induced the translocation of PS to the surface of platelets and microparticles, but failed to expose cFXIII.
Conclusion(s): The elevation of intracellular Ca2+ concentration is sufficient for the translocation of PS from the internal layer of the membrane, while the translocation of cFXIII from the platelet cytoplasm requires additional receptor mediated mechanism(s).
To cite this abstract in AMA style:Somodi L, Beke Debreceni I, Kis G, Cozzolino M, Kappelmayer J, Antal M, Panyi G, Bárdos H, Mutch N, Muszbek L. Surface exposure of cellular factor XIII on activated platelets and platelet microparticles is unrelated to the elevation of cytoplasmic Ca2+ concentration [abstract]. https://abstracts.isth.org/abstract/surface-exposure-of-cellular-factor-xiii-on-activated-platelets-and-platelet-microparticles-is-unrelated-to-the-elevation-of-cytoplasmic-ca2-concentration/. Accessed November 30, 2023.
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