L-Selectin-Mediated Leukocyte Adhesion and Migration Dynamics

L-selectin is a C-type lectin adhesion receptor expressed on most circulating leucocytes and constitutes the first molecular link between flowing cells and the vascular endothelium. By recognising specific glycan ligands on high endothelial venules and inflamed post‐capillary venules, L-selectin mediates transient tethering and rolling, thereby initiating the multi-step adhesion cascade. Beyond its adhesive role, force-dependent catch and slip bond transitions at the L-selectin–ligand interface transduce signals that regulate integrin activation, cytoskeletal rearrangement and directed migration. Fine‐tuned control of L-selectin function involves rapid ectodomain shedding, cytoplasmic interactions with ezrin-radixin-moesin proteins and calmodulin, and spatial positioning on microvilli. Together, these features ensure efficient leucocyte homing to lymphoid tissues, patrolling of the vasculature and timely recruitment to sites of infection or tissue injury, with broad implications for inflammatory disease, host defence and therapeutic intervention.

Research from Nature Portfolio

Recent studies have demonstrated how L‐selectin mechanochemistry restricts neutrophil priming in vivo. Mice expressing a mutant L‐selectin with altered catch bond behaviour exhibited prolonged bond lifetimes at low shear forces, leading to unstable leucocyte aggregates and exaggerated activation in response to inflammatory mediators. By dissecting the force‐dependent transitions between catch and slip states at the single‐molecule level under physiological flow, this work reveals that precise mechanochemical tuning of L‐selectin–ligand interactions preserves vascular homeostasis by preventing premature neutrophil activation and collateral tissue damage.

L-Selectin-Mediated Leukocyte Adhesion and Migration Dynamics publication trend

The graph below shows the total number of articles in l-selectin-mediated leukocyte adhesion and migration dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

L-selectin: A calcium-dependent lectin adhesion receptor on circulating leucocytes that initiates tethering and rolling on endothelial surfaces.

Leucocyte rolling: The transient, flow‐dependent interaction of L-selectin with endothelial ligands that slows cells and enables firm adhesion.

Transendothelial migration (TEM): The process by which leucocytes cross the endothelial barrier to enter tissues at sites of inflammation.

Catch/slip bonds: Force-modulated receptor–ligand interactions that either stabilise (catch) or destabilise (slip) bond lifetimes under mechanical load.

Ectodomain shedding: Proteolytic cleavage of the extracellular portion of L-selectin, regulating adhesive strength and downstream signalling pathways.

References

1. L-selectin mechanochemistry restricts neutrophil priming in vivo. Nature Communications (2017).
2. L-selectin: A Major Regulator of Leukocyte Adhesion, Migration and Signaling. Frontiers in Immunology (2019).
3. L-selectin regulates human neutrophil transendothelial migration. Journal of Cell Science (2021).
4. In Vitro and in Vivo Characterization of Molecular Interactions between Calmodulin, Ezrin/Radixin/Moesin, and L-selectin*. Journal of Biological Chemistry (2009).