Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α
- Max Planck Institute of Molecular Biomedicine, Germany
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.
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Author details
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.
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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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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