The procoagulant activity of apoptotic cells is mediated by interaction with factor XII

Aizhen Yang, Fengwu Chen, Chao He, Junsong Zhou, Yi Lu, Jihong Dai, Raymond B. Birge, Yi Wu

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Apoptotic cells, by externalizing phosphatidylserine (PS) as a hallmark feature, are procoagulant. However, the mechanism by which apoptotic cells activate coagulation system remains unknown. Intrinsic coagulation pathway is initiated by coagulation factor XII (FXII) of contact activation system. The purpose of this study was to determine whether FXII is involved in procoagulant activity of apoptotic cells. Using western blotting and chromogenic substrate assay, we found that incubation with apoptotic cells, but not with viable cells, resulted in rapid cleavage and activation of FXII in the presence of prekallikrein and high molecular weight kininogen (HK), other two components of contact activation system. As detected by flow cytometry, FXII bound to apoptotic cells in a concentration-dependent manner, which was inhibited by annexin V and PS liposome. Direct association of FXII with PS was confirmed in a surface plasmon resonance assay. Clotting time of FXII-deficient plasma induced by apoptotic cells was significantly prolonged, which was fully reversed by replenishment with FXII. Corn trypsin inhibitor, a FXII inhibitor, completely prevented apoptotic cells-induced intrinsic tenase complex formation. Consistently, apoptotic cells significantly increased thrombin production in normal plasma, which was not affected by an inhibitory anti-tissue factor antibody. However, blocking of PS by annexin V, inhibition of FXII, or the deficiency of FXII suppressed apoptotic cells-induced thrombin generation. Addition of purified FXII to FXII-deficient plasma recovered thrombin generation to the normal plasma level. In conclusion, FXII binds to apoptotic cells via PS and becomes activated, thereby constituting a novel mechanism mediating the procoagulant activity of apoptotic cells.

Original languageEnglish (US)
Article number1188
JournalFrontiers in immunology
Volume8
Issue numberSEP
DOIs
StatePublished - Sep 25 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

  • Apoptotic cells
  • Coagulation
  • Contact activation system
  • Factor XII
  • Phosphatidylserine

Fingerprint

Dive into the research topics of 'The procoagulant activity of apoptotic cells is mediated by interaction with factor XII'. Together they form a unique fingerprint.

Cite this