Leukocyte Transendothelial Migration Mechanisms

Leukocyte transendothelial migration is a coordinated multi-step process by which immune cells exit the bloodstream to reach sites of inflammation or injury. Initially, leukocytes tether and roll along the endothelium through selectin-mediated interactions. Firm adhesion follows via integrin engagement of endothelial ligands such as ICAM-1 and VCAM-1. Adherent cells then crawl to permissive sites and penetrate the vessel wall either paracellularly—at inter-endothelial junctions—or transcellularly—through individual endothelial cells. Endothelial signalling cascades involving small GTPases (for example RhoA), cytoskeletal remodelling and mechanosensitive channels preserve barrier integrity by forming contractile actin structures around transmigration pores. Anatomical and biomechanical heterogeneity among vascular beds further shapes the preferred migratory route, with profound implications for inflammatory disease and tissue homeostasis.

Research from Nature Portfolio

Studies have revealed that the balance between paracellular and transcellular routes varies markedly across vascular beds. In venules supplying the omentum, high expression of ICAM-1 and distinct endothelial stiffness promote transcellular neutrophil diapedesis when junctional adhesion is obstructed, whereas adjacent tissues rely chiefly on junctional passage. Complementary work has unpicked the fundamental mechanism by which endothelial cells confine transmigration pores. Local activation of RhoA via ICAM-1 clustering and associated Rho guanine-exchange factors drives assembly of contractile F-actin rings that encircle emigrating leukocytes, preventing plasma leakage and preserving vascular integrity during immune surveillance.

Leukocyte Transendothelial Migration Mechanisms publication trend

The graph below shows the total number of articles in leukocyte transendothelial migration mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Paracellular: Migration between adjacent endothelial cells at junctions.

Transcellular: Migration through the cytoplasm of individual endothelial cells.

Diapedesis: The passage of blood cells through the endothelial wall.

ICAM-1: Intercellular adhesion molecule-1, an endothelial ligand for leukocyte integrins.

VE-cadherin: Vascular endothelial cadherin, a key junctional adhesion protein.

RhoA: A small GTPase that regulates actin cytoskeleton dynamics.

Mechanosensation: Cellular detection of mechanical forces such as shear stress.

Filopodia: Thin, actin-rich protrusions involved in cell–cell interactions.

References

1. Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation. Mediators of Inflammation (2015).
2. Conditions that promote transcellular neutrophil migration in vivo. Scientific Reports (2024).
3. F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling. Nature Communications (2016).
4. Tension at the gate: sensing mechanical forces at the blood–brain barrier in health and disease. Journal of Neuroinflammation (2024).
5. Primary adhered neutrophils increase JNK1-MARCKSL1-mediated filopodia to promote secondary neutrophil transmigration. iScience (2023).
6. Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis. Blood (2022).