Abstract Number: PB0260
Meeting: ISTH 2020 Congress
Background: Inorganic polyphosphate (polyP) is abundantly found in every cell in nature and acts as phosphate and energy storage molecule. PolyP released from platelet granules initiates FXII-driven contact activation. The contribution of polyP from other immune cells is unknown.
Aims: To analyze plasma contact activation mediated by polyP derived from CD4+ T cells.
Methods: We quantified and compared polyP levels from different CD4+ T cell subsets using negative DAPI staining and malachite green assays. Stimulation and activation of T cells in vitro was performed to study mechanisms that increase polyP levels and mediate its release. We utilized chromogenic substrate cleavage assays to analyze contact activation by T-cell derived polyP.
Results: We found that pro-coagulant polyP increases in T cell antigen receptor stimulated CD4+ T cells. Inhibition of mitochondrial oxidative phosphorylation decreased intracellular polyP levels in CD4+ T cells. Comparison of T cell subsets ex vivo revealed that polyP levels are higher in anti-inflammatory CD4+CD25+ T cells than in naive CD4+CD25- T cells. Moreover, preliminary data showed that T cell differentiation and T cell polyP levels mutually control each other. To assess the contribution of T cell polyP for contact activation, we tested the capacity of T cell polyP to initiate FXII activation. We found that isolated T cell polyP in cell-free systems as well as polyP released from activated T cells promote FXII activation in vitro.
Conclusions: The accumulation of polyP in T cell antigen receptor stimulated CD4+ T cells and the activation-dependent release of T cell polyP indicates that CD4+ T cells may play a role in polyP-mediated contact activation. Further studies will reveal the potential implication of T cell polyP for thrombotic diseases.
To cite this abstract in AMA style:Mailer RK, Renné T. Plasma Contact Activation through T Cell-Derived Polyphosphate [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/plasma-contact-activation-through-t-cell-derived-polyphosphate/. Accessed May 6, 2021.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/plasma-contact-activation-through-t-cell-derived-polyphosphate/