Cellular FXIII in Human Macrophage-Derived Foam Cells
- Int J Mol Sci. 2023 Mar 2;24(5):4802. doi: 10.3390/ijms24054802.
- 1. Division of Clinical Laboratory Science, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, 4032 Debrecen, Hungary.
- 2. Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, 98 Nagyerdei krt, 4032 Debrecen, Hungary.
- 3. Pathology Service, County Emergency Clinical Hospital of Targu Mures, 50 Gheorghe Marinescu Street, 540136 Targu Mures, Romania.
- 4. Department of Pathology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 38 Gheorghe Marinescu Street, 540142 Targu Mures, Romania.
- 5. Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 26 Kassai út, 4028 Debrecen, Hungary.
- 6. Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, 4032 Debrecen, Hungary.
- 7. ELKH-UD Vascular Pathophysiology Research Group 11003, University of Debrecen, 4032 Debrecen, Hungary.
- 8. Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Macrophages express the A subunit of coagulation factor XIII (FXIII-A), a Transglutaminase which cross-links proteins through Nε-(γ-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque; they may stabilize the plaque by cross-linking structural proteins and they may become transformed into foam cells by accumulating oxidized LDL (oxLDL). The combination of oxLDL staining by Oil Red O and immunofluorescent staining for FXIII-A demonstrated that FXIII-A is retained during the transformation of cultured human Macrophages into foam cells. ELISA and Western blotting techniques revealed that the transformation of Macrophages into foam cells elevated the intracellular FXIII-A content. This phenomenon seems specific for macrophage-derived foam cells; the transformation of vascular smooth muscle cells into foam cells fails to induce a similar effect. FXIII-A containing Macrophages are abundant in the atherosclerotic plaque and FXIII-A is also present in the extracellular compartment. The protein cross-linking activity of FXIII-A in the plaque was demonstrated using an antibody labeling the iso-peptide bonds. Cells showing combined staining for FXIII-A and oxLDL in tissue sections demonstrated that FXIII-A-containing Macrophages within the atherosclerotic plaque are also transformed into foam cells. Such cells may contribute to the formation of lipid core and the plaque structurization.