Background: The dimer of potentially active A subunits of coagulation factor XIII (FXIII-A₂) also represents an intracellular component in a number of cells, including monocytes and monocyte derived macrophages. In contrast to plasma FXIII, cFXIII (cFXIII) does not need proteolysis for activation, elevation of intracellular Ca²⁺ concentration is sufficient to transform it into an active transglutaminase that catalyzes the cross-linking of peptide chains though e(g-glutamyl)lysyl bonds. cFXIII of monocytes is involved in the phagocytosis and if released from damaged cells or exposed to the cell surface it might be implicated in several physio-pathological processes.

Aims: To evaluate if foam cells transformed from cultured human macrophages retain their cFXIII content, and if yes, how their intracellular localization relates to that of oxidized low-density lipoprotein (oxLDL) particles. To monitor the intracellular content of cFXIII during the formation and maturation of foam cells.

Methods: Monocytes were differentiated into macrophages in the presence of 10 µg/mL granulocyte-macrophage colony-stimulating factor for three days. Foam cells, were generated from macrophages by incubation with 50 µg/ml oxLDL. cFXIII content was measured daily by ELISA and Western blotting. Intracellular localization of cFXIII and oxLDL particles within foam cells was investigated with confocal laser scanning fluorescence microscopy.

Results: Cellular factor XIII (green) and oxidized LDL (red) in several human macrophage derived foam cells. Nuclei are stained by DAPI (blue).

Macrophages contained a considerable amount of cFXIII (55.2 ng/10⁶ cells). Macrophages transformed into foam cells by feeding them with oxLDL particles retained cFXIII. 24 hours after introduction of LDL particles into the medium cFXIII content of macrophages more than doubled, then in the next two days only a slight decrease could be observed. cFXIII remained of cytoplasmic localization and did not overlap the LDL particles (Figure 1).  

Conclusions: cFXIII content of macrophages is considerably increased by their transformation into foam cells. cFXIII of foam cells, if externalized or released from damaged cells might contribute to the maturation of atherosclerotic plaque.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/cellular-factor-xiii-in-macrophage-derived-foam-cells/