Extracellular vesicles from human saliva promote hemostasis by delivering coagulant tissue factor to activated platelets

J Thromb Haemost. 2018 Jun;16(6):1153-1163. doi: 10.1111/jth.14023. Epub 2018 May 17.


Essentials Human salivary extracellular vesicles (EVs) expose coagulant tissue factor (TF). Salivary EVs expose CD24, a ligand of P-selectin. CD24 and coagulant TF co-localize on salivary EVs. TF+ /CD24+ salivary EVs bind to activated platelets and trigger coagulation.

Summary: Background Extracellular vesicles (EVs) from human saliva expose coagulant tissue factor (TF). Whether such TF-exposing EVs contribute to hemostasis, however, is unknown. Recently, in a mice model, tumor cell-derived EVs were shown to deliver coagulant TF to activated platelets at a site of vascular injury via interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin. Objectives We hypothesized that salivary EVs may deliver coagulant TF to activated platelets via interaction with P-selectin. Methods We investigated the presence of two ligands of P-selectin on salivary EVs, PSGL-1 and CD24. Results Salivary EVs expose CD24 but PSGL-1 was not detected. Immune depletion of CD24-exposing EVs completely abolished the TF-dependent coagulant activity of cell-free saliva, showing that coagulant TF and CD24 co-localize on salivary EVs. In a whole blood perfusion model, salivary EVs accumulated at the surface of activated platelets and promoted fibrin generation, which was abolished by an inhibitory antibody against human CD24. Conclusions A subset of EVs in human saliva expose coagulant TF and CD24, a ligand of P-selectin, suggesting that such EVs may facilitate hemostasis at a site of skin injury where the wound is licked in a reflex action.

Keywords: P-selectin; coagulation; extracellular vesicles; saliva; tissue factor.

MeSH terms

  • Blood Coagulation*
  • Blood Platelets / metabolism*
  • CD24 Antigen / metabolism
  • Extracellular Vesicles / metabolism*
  • Humans
  • Ligands
  • P-Selectin / metabolism
  • Platelet Activation*
  • Saliva / cytology
  • Saliva / metabolism*
  • Signal Transduction
  • Thromboplastin / metabolism*


  • CD24 Antigen
  • CD24 protein, human
  • Ligands
  • P-Selectin
  • SELP protein, human
  • Thromboplastin