Monocytes Expose Factor XIII-A and Stabilize Thrombi against Fibrinolytic Degradation

Fahad S. M. Alshehri, Claire S. Whyte, Ahmet Tuncay, Maria-Louise Williams, Heather M. Wilson, Nicola J. Mutch* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number6591
Number of pages15
Journal International Journal of Molecular Sciences
Volume22
Issue number12
Early online date19 Jun 2021
DOIs
Publication statusPublished - Jun 2021

Keywords

  • factor XIII-A
  • fibrinolysis
  • monocytes
  • thrombi
  • transglutaminase
  • cross-linking

Fingerprint

Dive into the research topics of 'Monocytes Expose Factor XIII-A and Stabilize Thrombi against Fibrinolytic Degradation'. Together they form a unique fingerprint.

Cite this