Neutrophil transendothelial migration hotspots - mechanisms and implications

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• Leukocyte transendothelial migration (TEM) is crucial for immune response during inflammation.
• The process involves sequential steps: rolling, adhesion, crawling, diapedesis, and sub-endothelial migration.
• Recent research highlights the endothelium's active role in directing leukocyte exit.

Purpose of the Study:

• To review the concept of transmigration hotspots.
• To discuss the biological relevance of these specific leukocyte exit sites.
• To identify factors contributing to the formation and function of TEM hotspots.

Main Methods:

• Review of existing literature on leukocyte transmigration.
• Analysis of factors influencing endothelial and pericyte layer interactions.
• Synthesis of mechanisms governing hotspot formation.

Main Results:

• Leukocyte exit sites are not random but are specific "transmigration hotspots."
• Hotspots are influenced by chemokine cues, adhesion molecules, and membrane protrusions.
• Physical factors like endothelial junction stability, substrate stiffness, pericytes, and basement membrane composition also shape hotspot formation.

Conclusions:

• Transmigration hotspots are critical regulatory sites for leukocyte extravasation.
• Understanding these hotspots provides insight into immune cell trafficking and inflammatory responses.
• Multiple molecular and physical cues converge to establish functional TEM hotspots.