Leukocytes use endothelial membrane tunnels to extravasate the vasculature
Upon inflammation, leukocytes extravasate through endothelial cells. When they extravasate, it is generally accepted that neighboring endothelial cells disconnect. Careful examination of endothelial junctions showed a partial membrane overlap beyond VE-cadherin distribution. These overlaps are regulated by actin polymerization and, although marked by, do not require PECAM-1, nor VE-cadherin. Neutrophils prefer wider membrane overlaps as exit sites. Detailed 3D analysis of neutrophil transmigration in real time at high spatiotemporal resolution revealed that overlapping endothelial membranes form a tunnel during neutrophil transmigration. These tunnels are formed by the neutrophil lifting the membrane of the upper endothelial cell while indenting and crawling over the membrane of the underlying endothelial cell. Our work shows that endothelial cells do not simply retract upon the passage of neutrophils but provide membrane tunnels, allowing neutrophils to extravasate. This discovery defines the 3D multicellular architecture in which the paracellular transmigration of neutrophils occurs.
Authors
- Amber J. M. Driessen (ORCID: https://orcid.org/0000-0002-5420-4258)
- Eike K. Mahlandt (ORCID: https://orcid.org/0000-0001-9458-8543)
- Reinier A. Boon (ORCID: https://orcid.org/0000-0001-7944-9748)
- Werner J. van der Meer (ORCID: https://orcid.org/0000-0002-0380-1722)
- Loïc Rolas (ORCID: https://orcid.org/0000-0001-7617-0768)
- Haitao Wang (ORCID: https://orcid.org/0000-0003-2340-0739)
- Sussan Nourshargh (ORCID: https://orcid.org/0000-0001-5677-1806)
- Rianne M. Schoon (ORCID: https://orcid.org/0000-0002-2609-9841)
- Jos van Rijssel (ORCID: https://orcid.org/0000-0001-8077-1371)
- Eric Wait (ORCID: https://orcid.org/0000-0002-1614-9219)
- John M. Heddleston (ORCID: https://orcid.org/0000-0002-9289-4114)
- Martijn A. Nolte (ORCID: https://orcid.org/0000-0002-5447-0839)
- Teng‐Leong Chew (ORCID: https://orcid.org/0000-0002-3139-7560)
- Lanette Kempers (ORCID: https://orcid.org/0000-0002-3298-0141)
- Reinier O. Schlingemann (ORCID: https://orcid.org/0000-0002-2300-8289)
- Abraham C.I. van Steen (ORCID: https://orcid.org/0000-0002-8023-352X)
- Max L.B. Grönloh (ORCID: https://orcid.org/0000-0003-0109-8225)
- Yosif Manavski
- Mark Hoogenboezem
- Joachim Goedhart (ORCID: https://orcid.org/0000-0002-0630-3825)
- Jaap D. van Buul (ORCID: https://orcid.org/0000-0003-0054-7949)
- Ingeborg Klaassen (ORCID: https://orcid.org/0000-0003-1695-9403)
- Satya Khuon (ORCID: https://orcid.org/0009-0009-9229-1530)
- Janine Arts
Institutions
- Howard Hughes Medical Institute (US)
- Janelia Research Campus (US)
- Imaging Center (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116242
- Citations
- 1
- Primary Topic
- Cell Adhesion Molecules Research
- Type
- article
- Field-Weighted Citation Impact
- 1.62