Work

Organized spatial patterns of activated β 2 integrins in arresting neutrophils

Year: 2018

Type: preprint

Abstract: The transition from leukocyte rolling to firm adhesion is called arrest. β 2 integrins are required for neutrophil arrest 1 . Chemokines can trigger neutrophil arrest in vivo 2 and in vitro 3 . Resting integrins 4 exist in a “bent-closed” conformation, i.e., not extended (E − ) and not high affinity (H − ), unable to bind ligand. Electron microscopic images of isolated β 2 integrins in “open” and “closed” conformations 5 inspired the switchblade model of integrin activation from E − H − to E + H − to E + H + 6 7 . Recently 8 , we discovered an alternative pathway of integrin activation from E − H − to E − H + to E + H + . Spatial patterning of activated integrins is thought to be required for effective arrest, but so far only diffraction-limited localization maps of activated integrins exist 8 . Here, we combine superresolution microscopy with molecular modeling to identify the molecular patterns of H + E − , H − E + , and H + E + activated integrins on primary human neutrophils. At the time of neutrophil arrest, E + H + integrins form oriented (non-random) nanoclusters that contain a total of 4,625±369 E + H + β 2 integrin molecules.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.1101/323279