Cyclic stretch enhances neutrophil extracellular trap formation.

Area of Science:

• Immunology
• Biomedical Engineering
• Cell Biology

Background:

• Neutrophils are key immune cells involved in host defense and inflammatory disorders.
• Neutrophil extracellular traps (NETs) are crucial for pathogen capture but excessive NETosis contributes to thrombosis.
• The influence of mechanical forces on neutrophil function, particularly NETosis, remains largely unexplored.

Purpose of the Study:

• To investigate the interactive effects of substrate stiffness and cyclic stretch on neutrophil extracellular trap formation (NETosis).
• To understand how mechanical cues from the tissue microenvironment modulate neutrophil behavior.

Main Methods:

• Primary neutrophils were cultured on substrates with varying stiffness (30 and 300 kPa).
• Neutrophils were subjected to static conditions or cyclic stretch (5% and 10%).
• NETosis induction was assessed using agents like PMA, ATP, and LPS.

Main Results:

• Increased substrate stiffness and cyclic stretch enhanced neutrophil nuclear decondensation and histone H3 citrullination.
• Mechanical forces amplified neutrophil responses to NET-inducing agents.
• Stretch-induced neutrophil activation involved calpain activity, PI3K/FAK signaling, and actin polymerization.

Conclusions:

• Mechanical forces from the tissue microenvironment significantly influence NETosis.
• This study identifies mechanical cues as critical regulators of neutrophil function.
• Modulating mechanical forces presents a potential novel therapeutic strategy for NETosis-related conditions.