Abstract
The LFA-1 integrin is crucial for the firm adhesion of circulating leukocytes to ICAM-1-expressing endothelial cells. In the present study, we demonstrate that LFA-1 can arrest unstimulated PBL subsets and lymphoblastoid Jurkat cells on immobilized ICAM-1 under subphysiological shear flow and mediate firm adhesion to ICAM-1 after short static contact. However, LFA-1 expressed in K562 cells failed to support firm adhesion to ICAM-1 but instead mediated K562 cell rolling on the endothelial ligand under physiological shear stress. LFA-1-mediated rolling required an intact LFA-1 I-domain, was enhanced by Mg2+, and was sharply dependent on ICAM-1 density. This is the first indication that LFA-1 can engage in rolling adhesions with ICAM-1 under physiological shear flow. The ability of LFA-1 to support rolling correlates with decreased avidity and impaired time-dependent adhesion strengthening. A beta2 cytoplasmic domain-deletion mutant of LFA-1, with high avidity to immobilized ICAM-1, mediated firm arrests of K562 cells interacting with ICAM-1 under shear flow. Our results suggest that restrictions in LFA-1 clustering mediated by cytoskeletal attachments may lock the integrin into low-avidity states in particular cellular environments. Although low-avidity LFA-1 states fail to undergo adhesion strengthening upon contact with ICAM-1 at stasis, these states are permissive for leukocyte rolling on ICAM-1 under physiological shear flow. Rolling mediated by low-avidity LFA-1 interactions with ICAM-1 may stabilize rolling initiated by specialized vascular rolling receptors and allow the leukocyte to arrest on vascular endothelium upon exposure to stimulatory endothelial signals.
Original language | English |
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Pages (from-to) | 442-52 |
Number of pages | 11 |
Journal | Journal of Immunology |
Volume | 165 |
Issue number | 1 |
Publication status | Published - 1 Jul 2000 |
Keywords
- Cations, Divalent/pharmacology
- Cell Adhesion/genetics
- Cell Communication/genetics
- Cell Movement/genetics
- Humans
- Intercellular Adhesion Molecule-1/metabolism
- Jurkat Cells
- K562 Cells/metabolism
- Lymphocyte Function-Associated Antigen-1/genetics
- Lymphocytes
- Microscopy, Confocal
- Microscopy, Phase-Contrast
- Microscopy, Video
- Protein Binding/immunology
- Rheology
- Sequence Deletion/immunology
- Stress, Mechanical
- T-Lymphocytes/immunology