Ligand-specific binding forces of LFA-1 and Mac-1 in neutrophil adhesion and crawling

Lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) and their counterreceptors such as intercellular cell adhesion molecules (ICAM-1 and ICAM-2), junctional adhesion molecules (JAM-A, JAM-C), and receptors for advanced glycation end products (RAGE) are crucial for promo...

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Bibliographic Details
Published in:Molecular biology of the cell 2018-02, Vol.29 (4), p.408-418
Main Authors: Li, Ning, Yang, Hao, Wang, Manliu, Lü, Shouqin, Zhang, Yan, Long, Mian
Format: Article
Language:English
Subjects:
Animals
CD18 Antigens - metabolism
Cell Adhesion - physiology
Cell Movement - physiology
Humans
Intercellular Adhesion Molecule-1 - metabolism
Ligands
Lymphocyte Function-Associated Antigen-1 - metabolism
Macrophage-1 Antigen - metabolism
Male
Mice
Mice, Inbred C57BL
Microscopy, Atomic Force
Neutrophils - metabolism
Signal Transduction
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Summary:Lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) and their counterreceptors such as intercellular cell adhesion molecules (ICAM-1 and ICAM-2), junctional adhesion molecules (JAM-A, JAM-C), and receptors for advanced glycation end products (RAGE) are crucial for promoting polymorphonuclear leukocyte (neutrophil, PMN) recruitment. The underlying mechanisms of ligand-specific bindings in this cascade remain incompletely known. We compared the dynamic force spectra for various LFA-1/Mac-1-ligand bonds using single-molecule atomic force microscopy (AFM) and tested their functions in mediating PMN recruitment under in vitro shear flow. Distinct features of bond rupture forces and lifetimes were uncovered for these ligands, implying their diverse roles in regulating PMN adhesion on endothelium. LFA-1 dominates PMN adhesion on ICAM-1 and ICAM-2, while Mac-1 mediates PMN adhesion on RAGE, JAM-A, and JAM-C, which is consistent with their bond strength. All ligands can trigger PMN spreading and polarization, in which Mac-1 seems to induce outside-in signaling more effectively. LFA-1-ICAM-1 and LFA-1/Mac-1-JAM-C bonds can accelerate PMN crawling under high shear stress, presumably due to their high mechanical strength. This work provides new insight into basic molecular mechanisms of physiological ligands of β2 integrins in PMN recruitment.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E16-12-0827