Endothelial cell autophagy keeps neutrophil trafficking under control

Area of Science:

• Immunology
• Cell Biology

Background:

• Neutrophil infiltration into tissues is a hallmark of inflammation, requiring passage through endothelial cells (ECs).
• Molecular mechanisms terminating neutrophil breaching of venular walls are not fully understood.
• Dysregulated neutrophil trafficking contributes to various pathologies.

Purpose of the Study:

• To identify molecular mechanisms that regulate the termination of neutrophil breaching of venular walls.
• To investigate the role of endothelial cell (EC) autophagy in neutrophil diapedesis during acute inflammation.

Main Methods:

• Utilized in vivo models to study neutrophil trafficking and endothelial cell autophagy.
• Employed genetic ablation of EC autophagy and pharmacological induction.
• Analyzed the impact on neutrophil transendothelial migration (TEM) and tissue infiltration.

Main Results:

• Inflamed venular ECs upregulate autophagy, localized to EC contacts and temporally aligned with neutrophil trafficking.
• Genetic ablation of EC autophagy resulted in excessive neutrophil infiltration and enhanced TEM.
• Pharmacological induction of autophagy inhibited neutrophil migration.

Conclusions:

• Endothelial cell (EC) autophagy acts as a negative regulator of neutrophil diapedesis in acute physiological inflammation.
• Autophagy machinery controls EC contact architecture and adhesion molecule dynamics, serving as a physiological brake on leukocyte trafficking.