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

Abstract:

: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.

journal_name

Mol Biol Cell

authors

Li N,Yang H,Wang M,Lü S,Zhang Y,Long M

doi

10.1091/mbc.E16-12-0827

subject

Has Abstract

pub_date

2018-02-15 00:00:00

pages

408-418

issue

4

eissn

1059-1524

issn

1939-4586

pii

mbc.E16-12-0827

journal_volume

29

pub_type

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