Monocytes Expose Factor XIII-A and Stabilize Thrombi against Fibrinolytic Degradation
| Autor: | Nicola J. Mutch, Heather M. Wilson, Fahad S. M. Alshehri, Maria-Louise Williams, Claire S. Whyte, Ahmet Tuncay |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Lipopolysaccharide THP-1 Cells QH301-705.5 Stimulation 030204 cardiovascular system & hematology factor XIII-A Catalysis Fibrin Article Flow cytometry Inorganic Chemistry 03 medical and health sciences chemistry.chemical_compound transglutaminase 0302 clinical medicine Antigen medicine Humans Platelet activation Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy biology medicine.diagnostic_test Organic Chemistry Thrombosis General Medicine Factor XIII thrombi Healthy Volunteers Computer Science Applications Cell biology Chemistry 030104 developmental biology chemistry biology.protein fibrinolysis Factor XIIIa monocytes Intracellular medicine.drug cross-linking |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 6591, p 6591 (2021) International Journal of Molecular Sciences Volume 22 Issue 12 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Factor XIII (FXIII) is a transglutaminase that promotes thrombus stability by cross-linking fibrin. The cellular form, a homodimer of the A subunits, denoted FXIII-A, lacks a classical signal peptide for its release however, we have shown that it is exposed on activated platelets. Here we addressed whether monocytes expose intracellular FXIII-A in response to stimuli. Using flow cytometry, we demonstrate that FXIII-A antigen and activity are up-regulated on human monocytes in response to stimulation by IL-4 and IL-10. Higher basal levels of the FXIII-A antigen were noted on the membrane of the monocytic cell line THP-1, but activity was significantly enhanced following stimulation with IL-4 and IL-10. In contrast, treatment with lipopolysaccharide did not upregulate exposure of FXIII-A in THP-1 cells. Quantification of the FXIII-A activity revealed a significant increase in THP-1 cells in total cell lysates following stimulation with IL-4 and IL-10. Following fractionation, the largest pool of FXIII-A was membrane associated. Monocytes were actively incorporated into the fibrin mesh of model thrombi. We found that stimulation of monocytes and THP-1 cells with IL-4 and IL-10 stabilized FXIII-depleted thrombi against fibrinolytic degradation, via a transglutaminase-dependent mechanism. Our data suggest that monocyte-derived FXIII-A externalized in response to stimuli participates in thrombus stabilization. |
| Databáze: | OpenAIRE |
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