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Factor XII in coagulation, inflammation and beyond.

Miroslava Didiasova1, Lukasz Wujak1, Liliana Schaefer2

  • 1Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Giessen, Germany.

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Summary

Factor XII (FXII) is a protease involved in blood clotting and inflammation. Emerging research indicates FXII directly regulates cellular responses, impacting processes like neuroinflammation and wound healing.

Keywords:
BradykininCoagulation factor XIIIntrinsic blood coagulationKallikrein-kinin system

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Area of Science:

  • Biochemistry
  • Hematology
  • Immunology

Background:

  • Factor XII (FXII) is a plasma protease zymogen activated by negatively charged surfaces.
  • FXIIa initiates intrinsic coagulation, the kallikrein-kinin system, fibrinolysis, and complement activation.
  • Evidence suggests FXII/FXIIa directly influences cellular functions beyond its enzymatic activities.

Purpose of the Study:

  • To review the direct cellular effects of Factor XII and its active form, FXIIa.
  • To explore the mechanisms by which FXII/FXIIa regulates cellular responses.
  • To highlight the implications of these direct cellular interactions in various physiological and pathological conditions.

Main Methods:

  • Literature review of studies investigating Factor XII's role in cellular processes.
  • Analysis of experimental data demonstrating FXII/FXIIa-induced cellular responses.
  • Synthesis of findings related to genetic ablation studies and in vitro cell-based assays.

Main Results:

  • FXII/FXIIa induces inflammatory mediators, cell proliferation, and migration of immune and fibroblast cells.
  • Genetic deletion of FXII confers protection against neuroinflammation and atherosclerosis.
  • FXII deficiency improves wound healing and inhibits postnatal angiogenesis.

Conclusions:

  • Factor XII possesses direct cellular regulatory functions independent of its proteolytic activity.
  • These direct cellular effects contribute to inflammation, wound healing, and vascular development.
  • Understanding FXII's direct cellular roles offers new therapeutic targets for related diseases.