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bioRxiv · 10.1101/323279

Organized spatial patterns of activated β2 integrins in arresting neutrophils

Fan, Z.·Kiosses, W. B.·Zajonc, D. M.·Arnaout, M. A.·Gutierrez, E.·Groisman, A.·Ley, K.
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Abstract

The transition from leukocyte rolling to firm adhesion is called arrest. {beta}2 integrins are required for neutrophil arrest1. Chemokines can trigger neutrophil arrest in vivo2 and in vitro3. Resting integrins4 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 {beta}2 integrins in \"open\" and \"closed\" conformations5 inspired the switchblade model of integrin activation from E-H- to E+H- to E+H+67. Recently8, 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 exist8. 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+ {beta}2 integrin molecules.

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Fan, Z., Kiosses, W. B., Zajonc, D. M., Arnaout, M. A., Gutierrez, E., Groisman, A., Ley, K.. 2018-05-16. Organized spatial patterns of activated β2 integrins in arresting neutrophils. https://doi.org/10.1101/323279

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