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Front. Immunol. | doi: 10.3389/fimmu.2019.02011

Roles of Factor XII in Innate Immunity

  • 1Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Germany
  • 2Department of Medicine, Louis Stokes Cleveland VA Medical Center, United States
  • 3Department of Medicine, Case Western Reserve University, United States

Factor XII (FXII) is the zymogen of serine protease, factor XIIa (FXIIa). FXIIa enzymatic activities have been extensively studied and FXIIa inhibition is emerging as a promising target to treat or prevent thrombosis without creating a hemostatic defect. FXII and plasma prekallikrein reciprocally activate each other and result in liberation of bradykinin. Due to its unique structure among coagulation factors, FXII exerts mitogenic activity in endothelial and smooth muscle cells, indicating that zymogen FXII has activities independent of its protease function. A growing body of evidence has revealed that both FXII and FXIIa upregulate neutrophil functions, contribute to macrophage polarization and induce T-cell differentiation. In vivo, these signaling activities contribute to host defense against pathogens, mediate the development of neuroinflammation, influence wound repair and may facilitate cancer maintenance and progression. Here, we review the roles of FXII in innate immunity as they relate to non-sterile and sterile immune responses.

Keywords: uPAR, NETs (neutrophil extracellular traps, Sepsis, Contact activation, Contact Activation System, Wound Healing, Cancer Progression, Macrophages, factor XII (FXII)

Received: 14 Jun 2019; Accepted: 08 Aug 2019.

Edited by:

Krasimir Kolev, Semmelweis University, Hungary

Reviewed by:

Sven Hammerschmidt, University of Greifswald, Germany
Yi Wu, Temple U  

Copyright: © 2019 Renné and Stavrou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Evi X. Stavrou, Louis Stokes Cleveland VA Medical Center, Department of Medicine, Cleveland, 44106, Ohio, United States,