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Review
. 2018 Sep;25(5):403-409.
doi: 10.1097/MOH.0000000000000450.

Factor XII in inflammation and wound healing

Evi X Stavrou  1   2
Affiliations
Review

Factor XII in inflammation and wound healing

Evi X Stavrou. Curr Opin Hematol. 2018 Sep.

Abstract

Purpose of review: This review describes the contribution of coagulation factor XII (FXII) in sterile inflammation and wound healing, focusing on recently identified roles for zymogen FXII in neutrophil functions.

Recent findings: Recent studies have identified an important role for FXII in neutrophil trafficking. In particular, following neutrophil activation, autocrine FXII signals through the urokinase plasminogen activator receptor (uPAR) on the neutrophil surface to upregulate neutrophil functions. The sum of these activities leads to neutrophil adhesion, chemotaxis, and neutrophil extracellular (NET) formation. Downregulating FXII-mediated signaling in neutrophils is associated with improved wound healing.

Summary: These recent findings show the sophisticated role of FXII in vivo and create new opportunities for research on the treatment of chronic inflammatory diseases.

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Conflict of interest statement

CONFLICTS OF INTEREST

None

Figures

Figure 1:
Figure 1:. Role of FXII in inflammation and wound healing.
Following initial neutrophil activation, autocrine FXII and uPAR interact on the neutrophil surface to promote Akt2S474 phosphorylation. Propagation of FXII-mediated neutrophil activities leads to 1) surface expression of αMβ2 integrin, 2) increase in intracellular calcium (Ca2+), and 3) histone citrullination and extracellular (EC) DNA release. The sum of these activities sustains neutrophil proinflammatory responses and contributes to delayed wound healing. Neutrophil-derived FXII activities are distinct from plasma FXII functions of contact activation on the surface of preformed NETs. Areas of active investigation to further delineate the FXII-uPAR interactome are marked as “?”.
See this image and copyright information in PMC

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