Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α
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 neutro...
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doaj-4a4b4af82157476185072f0adc9acebd2021-05-05T17:49:01ZengeLife Sciences Publications LtdeLife2050-084X2019-08-01810.7554/eLife.47642Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-αYu-Tung Li0https://orcid.org/0000-0002-0718-7344Debashree Goswami1Melissa Follmer2Annette Artz3Mariana Pacheco-Blanco4Dietmar Vestweber5https://orcid.org/0000-0002-3517-732XVascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, GermanyVascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, GermanyVascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, GermanyVascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, GermanyVascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, GermanyVascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, GermanyArrest 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 β2-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.https://elifesciences.org/articles/47642leukocyte extravasationneutrophilsinflammationendotheliumintegrins |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu-Tung Li Debashree Goswami Melissa Follmer Annette Artz Mariana Pacheco-Blanco Dietmar Vestweber |
spellingShingle |
Yu-Tung Li Debashree Goswami Melissa Follmer Annette Artz Mariana Pacheco-Blanco Dietmar Vestweber Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α eLife leukocyte extravasation neutrophils inflammation endothelium integrins |
author_facet |
Yu-Tung Li Debashree Goswami Melissa Follmer Annette Artz Mariana Pacheco-Blanco Dietmar Vestweber |
author_sort |
Yu-Tung Li |
title |
Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α |
title_short |
Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α |
title_full |
Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α |
title_fullStr |
Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α |
title_full_unstemmed |
Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α |
title_sort |
blood flow guides sequential support of neutrophil arrest and diapedesis by pilr-β1 and pilr-α |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-08-01 |
description |
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 β2-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. |
topic |
leukocyte extravasation neutrophils inflammation endothelium integrins |
url |
https://elifesciences.org/articles/47642 |
work_keys_str_mv |
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