Abstract Number: LPB0112
Meeting: ISTH 2021 Congress
Background: Factor XIII (FXIII) is a transglutaminase (TG) that promotes thrombus stability by cross-linking fibrin. FXIII exists as a cellular form, a homodimer of the A subunits (FXIII-A) and it is found in abundance within circulating platelets and monocytes.
Aims: To investigate externalization of FXIII-A on monocytes and its role in extracellular crosslinking reactions.
Methods: Isolated human monocytes or THP-1 cells (6 x 105cells/ml) were treated ± 20 ng/ml interleukin-4 (IL-4); 20 ng/ml interleukin-10 (IL-10); or 100 ng/ml lipopolysaccharide (LPS) for 24 h. FXIII-A exposure and activity were detected using a FITC-labelled anti-FXIII-A antibody (40 μg/ml) or the fluorescent amine donor substrate, TAMRA (40 μg/ml) by flow cytometer and imaged by confocal microscopy. Pooled normal plasma or factor XIII deficient plasma + FITC-labelled fibrinogen (45 µg/ml) was re-calcified with CaCl2 (10.9 mM) ± stimulated monocytes or THP-1 cells (3 x 105 cells/ml) ± 1 mM a TG inhibitor. Thrombi were bathed in tissue plasminogen activator (1 µg/ml) and sampled every 30 min for 4 h and fluorescence read (Ex 485 nm Em 528 nm).
Results: IL-10 stimulation significantly increased the number of FXIII-A positive monocytes compared to unstimulated cells (21.2 ± 3.4% vs 7.9 ± 2.1% P < 0.05). FXIII-A activity was augmented 2.5-fold with IL-4 and IL-10 stimulation compared to resting cells. Basal levels of FXIII-A antigen expression were higher in THP-1 cells with a negligible impact of stimulation. However, FXIII-A activity on the surface of THP-1 cells was significantly increased with all stimuli compared to resting cells. FXIII-A antigen and activity were expressed on the external membrane of stimulated monocytes and THP-1 cells. However, the distribution with LPS stimulation produced a distinct punctate pattern around the cell periphery. IL-4 or IL-10 activated monocytes and THP-1 cells stabilized FXIII-depleted.
Conclusions: Activated monocytes and THP-1 cells externalize and retain active FXIII-A on their membrane thereby stabilizing thrombi against fibrinolytic degradation.
To cite this abstract in AMA style:Alshehri F. Monocytes Expose Factor XIII-A and Stabilize Thrombi against Fibrinolytic Degradation [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/monocytes-expose-factor-xiii-a-and-stabilize-thrombi-against-fibrinolytic-degradation/. Accessed December 11, 2023.
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