Agonist leukadherin-1 increases CD11b/CD18-dependent adhesion via membrane tethers.

ABSTRACT: Integrin CD11b/CD18 is a key adhesion receptor that mediates leukocyte migration and immune functions. Leukadherin-1 (LA1) is a small molecule agonist that enhances CD11b/CD18-dependent cell adhesion to its ligand ICAM-1. Here, we used single-molecule force spectroscopy to investigate the biophysical mechanism by which LA1-activated CD11b/CD18 mediates leukocyte adhesion. Between the two distinct populations of CD11b/CD18:ICAM-1 complex that participate in cell adhesion, the cytoskeleton(CSK)-anchored elastic elements and the membrane tethers, we found that LA1 enhanced binding of CD11b/CD18 on K562 cells to ICAM-1 via the formation of long membrane tethers, whereas Mn(2+) additionally increased ICAM-1 binding via CSK-anchored bonds. LA1 activated wild-type and LFA1(-/-) neutrophils also s

SUBMITTER: Celik E 

PROVIDER: S-EPMC3853324 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature