Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α

Abstract

Arrest of rapidly flowing neutrophils in venules relies on capturing through selectins and chemokine-induced integrin activation. Despite a long-established concept, we show here that gene inactivation of activating paired immunoglobulin-like receptor (PILR)-β1 nearly halved the efficiency of neutrophil arrest in venules of the mouse cremaster muscle. We found that this receptor binds to CD99, an interaction which relies on flow-induced shear forces and boosts chemokine-induced b2-integrin-activation, leading to neutrophil attachment to endothelium. Upon arrest, binding of PILR-β1 to CD99 ceases, shifting the signaling balance towards inhibitory PILR-α. This enables integrin deactivation and supports cell migration. Thus, flow-driven shear forces guide sequential signaling of first activating PILR-β1 followed by inhibitory PILR-α to prompt neutrophil arrest and then transmigration. This doubles the efficiency of selectin-chemokine driven neutrophil arrest by PILR-β1 and then supports transition to migration by PILR-α.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files for the figures have been provided.

Article and author information

Author details

  1. Yu-Tung Li

    Department of Vascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0718-7344
  2. Debashree Goswami

    Department of Vascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Melissa Follmer

    Department of Vascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Annette Artz

    Department of Vascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Mariana Pacheco-Blanco

    Department of Vascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Dietmar Vestweber

    Department of Vascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, Germany
    For correspondence
    vestweb@mpi-muenster.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3517-732X

Funding

Deutsche Forschungsgemeinschaft (SFB1009)

  • Debashree Goswami

Deutsche Forschungsgemeinschaft (A1)

  • Debashree Goswami

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were carried out under German legislation for the protection of animals and approved by the Landesamt für Natur Umwelt und Verbraucherschutz Nordrhein-Westfalen under the reference number AZ 84-02.04.2017.A101.

Reviewing Editor

  1. Reinhard Fässler, Max Planck Institute of Biochemistry, Germany

Version history

  1. Received: April 11, 2019
  2. Accepted: August 5, 2019
  3. Accepted Manuscript published: August 6, 2019 (version 1)
  4. Version of Record published: August 19, 2019 (version 2)

Copyright

© 2019, Li et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yu-Tung Li
  2. Debashree Goswami
  3. Melissa Follmer
  4. Annette Artz
  5. Mariana Pacheco-Blanco
  6. Dietmar Vestweber
(2019)
Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α
eLife 8:e47642.
https://doi.org/10.7554/eLife.47642

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https://doi.org/10.7554/eLife.47642

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