Neutrophil Extracellular Traps Affect Human Inner Ear Vascular Permeability

Area of Science:

• Inner ear physiology and pathology
• Vascular biology and endothelial function
• Immunology and inflammation

Background:

• The blood-labyrinth barrier (BLB) is crucial for maintaining inner ear homeostasis and preventing harmful substance entry.
• Dysregulation of BLB permeability is linked to various auditory pathologies, including acoustic trauma and autoimmune inner ear diseases.
• Neutrophil extracellular traps (NETs) are implicated in autoimmune and autoinflammatory conditions and modulate vascular permeability.

Purpose of the Study:

• To investigate the impact of NETs on a cellular model of the blood-labyrinth barrier (BLB).
• To assess how NETs affect endothelial permeability and junctional gene expression in inner ear endothelial cells.

Main Methods:

• Utilized a Transwell® cell culture system to model the BLB.
• Exposed human inner ear-derived endothelial cells to varying concentrations of NETs.
• Measured endothelial permeability markers, including transepithelial electrical resistance (TEER) and dextran permeability.
• Analyzed the expression of key junctional genes (ZO-1, OCL, CDH5) and observed cytoskeletal architecture.

Main Results:

• NETs demonstrated a concentration-dependent increase in endothelial permeability.
• Reduced TEER and enhanced dextran permeability indicated a compromised BLB.
• Downregulation of junctional gene expression (ZO-1, OCL, CDH5) and alterations in cytoskeletal structure were observed.

Conclusions:

• NETs significantly impair the integrity of the blood-labyrinth barrier in vitro.
• These findings suggest a potential role for NETs in the pathogenesis of BLB dysfunction and associated auditory disorders.
• Further research is warranted to explore therapeutic strategies targeting NETs for auditory health.