Avidity enhancement of L-selectin bonds by flow: shear-promoted rotation of leukocytes turn labile bonds into functional tethers.
L-selectin is a key lectin essential for leukocyte capture and rolling on vessel walls. Functional adhesion of L-selectin requires a minimal threshold of hydrodynamic shear. Using high temporal resolution videomicroscopy, we now report that L-selectin engages its ligands through exceptionally labile adhesive bonds (tethers) even below this shear threshold. These tethers share a lifetime of 4 ms on distinct physiological ligands, two orders of magnitude shorter than the lifetime of the P-selectin-PSGL-1 bond. Below threshold shear, tether duration is not shortened by elevated shear stresses. However, above the shear threshold, selectin tethers undergo 14-fold stabilization by shear-driven leukocyte transport. Notably, the cytoplasmic tail of L-selectin contributes to this stabilization only above the shear threshold. These properties are not shared by P-selectin- or VLA-4-mediated tethers. L-selectin tethers appear adapted to undergo rapid avidity enhancement by cellular transport, a specialized mechanism not used by any other known adhesion receptor.
Dwir
Oren
O
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Solomon
Ariel
A
Mangan
Shmuel
S
Kansas
Geoffrey S
GS
Schwarz
Ulrich S
US
Alon
Ronen
R
D001665:Binding Sites / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D008024:Ligands; D009077:Mucins / Q000378:metabolism; D013314:Stress, Mechanical
D039041:Integrin alpha4beta1; D008024:Ligands; D009077:Mucins; D019041:L-Selectin