Human β-Defensin-3 is Associated With Platelet-Derived Extracellular Vesicles and is a Potential Contributor to...

Area of Science:

• Immunology
• Hematology
• Vascular Biology

Background:

• Platelets are key in hemostasis and increasingly recognized for host defense roles.
• Human β-defensin 3 (hBD-3), an antimicrobial peptide, is typically produced by epithelial cells.

Purpose of the Study:

• To investigate the presence and function of hBD-3 within human platelets and platelet-derived extracellular vesicles (p-EVs).
• To determine the impact of hBD-3 and hBD-3-enriched p-EVs on endothelial cell function.

Main Methods:

• Immunofluorescent microscopy, western blot, ELISA, flow cytometry, and immuno-electron microscopy were used to detect hBD-3 in platelets and p-EVs.
• Platelet activation and endothelial cell dysfunction were assessed in vitro.
• Levels of phosphorylated endothelial nitric oxide synthase (eNOS), Krüppel like factor-2 (KLF-2), and von Willebrand Factor (vWF) were measured.

Main Results:

• hBD-3 was detected in human platelets, megakaryocytes, and on activated platelet surfaces.
• hBD-3 was found in platelet-derived extracellular vesicles (p-EVs).
• Exposure to hBD-3 or p-EVs induced endothelial dysfunction, characterized by reduced p-eNOS and KLF-2, and increased vWF. hBD-3 pre-incubation augmented this dysfunction.

Conclusions:

• Activated platelets release hBD-3-enriched EVs.
• These EVs contribute to endothelial dysfunction and may promote a pro-thrombotic state.
• This suggests a link between innate immunity and hemostasis via platelet-EV signaling.