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

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

Author information

1
Laboratory of Experimental Clinical Chemistry, Academic Medical Centre (AMC) of the University of Amsterdam, Amsterdam, the Netherlands.
2
Vesicle Observation Centre, AMC, Amsterdam, the Netherlands.
3
Department of Biomedical Engineering and Physics, AMC, Amsterdam, the Netherlands.
4
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.
5
Department of Medical Biology, Electron Microscopy Centre Amsterdam, AMC, Amsterdam, the Netherlands.
6
Skin Cancer Unit, German Cancer Research Center, Heidelberg, Germany.
7
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Heidelberg, Germany.

Abstract

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

PMID:
29658195
DOI:
10.1111/jth.14023
[Indexed for MEDLINE]

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