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Distinct molecular and cellular contributions to stabilizing selectin-mediated rolling under flow
Tadayuki Yago1, Anne Leppänen, Haiying Qiu
1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 74104, USA.
The Journal of Cell Biology
|August 15, 2002
Summary
Leukocyte rolling on selectins is more stable and shear-resistant than microsphere rolling. Cellular properties, not just ligand structure, are crucial for optimizing selectin-ligand interactions and stable cell adhesion.
Area of Science:
- Biophysics
- Cell Biology
- Immunology
Background:
- Leukocytes exhibit stable rolling on selectins, a process vital for immune surveillance.
- Understanding the factors governing leukocyte rolling is key to modulating immune cell trafficking.
Purpose of the Study:
- To differentiate the roles of ligand structure versus cellular properties in selectin-mediated leukocyte rolling.
- To investigate how cell deformability and ligand presentation influence rolling stability and shear resistance.
Main Methods:
- Coupling of selectin ligands (sPSGL-1, GSP-6) to microspheres and K562 cells.
- Comparison of rolling behavior on P-selectin under varying wall shear stresses.
- Manipulation of K562 cell properties (deformability, ligand presentation) using chemical treatments.
Main Results:
- Microspheres and K562 cells with randomly coupled ligands showed unstable, shear-sensitive rolling.
- K562 cells with membrane-targeted sPSGL-1 or GSP-6 exhibited leukocyte-like rolling: uniform, shear-resistant, and velocity-plateauing.
- Increased cell deformability (cytochalasin D) enhanced rolling stability and shear resistance.
Conclusions:
- Cellular properties, particularly deformability and organized ligand presentation, are critical for stable, shear-resistant selectin-mediated rolling.
- These findings highlight the importance of the cellular microenvironment in leukocyte adhesion dynamics.
- Optimized cell-ligand interactions, rather than ligand structure alone, dictate efficient leukocyte rolling.