Neutrophils Induce P-Selectin Shedding from Activated Platelets Via Neutrophil Elastase

Area of Science:

• Hematology
• Immunology
• Cell Biology

Background:

• Neutrophil adhesion to platelet P-selectin (P-sel) may trigger P-sel shedding, but the mechanism is unclear.
• Platelet P-selectin plays a role in cell adhesion and inflammatory responses.

Purpose of the Study:

• To investigate the role of neutrophils in platelet P-selectin shedding.
• To elucidate the mechanism by which neutrophils influence P-selectin shedding from activated platelets.

Main Methods:

• Platelets were activated with thrombin, collagen, or TRAP and co-cultured with neutrophils.
• Inhibitors of myeloperoxidase (MPO), neutrophil elastase (NE), and neutrophil extracellular traps (NETs) formation (Latrunculin B) were used.
• P-selectin expression, soluble P-selectin (sP-sel), and soluble NE levels were measured.

Main Results:

• Neutrophil-induced P-selectin shedding occurred specifically on thrombin-activated platelets.
• Neutrophil elastase (NE) within NETs appears to mediate P-selectin shedding.
• MPO inhibitors accelerated shedding, while NE inhibitors and LatB partially reversed it.

Conclusions:

• Neutrophil-induced platelet P-selectin shedding is mediated by concentrated NE in NETs.
• This process leads to irreversible functional downregulation of platelet P-selectin-mediated interactions.
• Platelet-neutrophil interactions are bidirectional, with thrombin-activated platelets promoting NET formation and neutrophils inducing platelet P-selectin shedding.