Lymphocyte Crawling and Transendothelial Migration Require Chemokine Triggering of High-Affinity LFA-1 Integrin
Open accessAbstract
Endothelial chemokines are instrumental for integrin-mediated lymphocyte adhesion and transendothelial migration (TEM). By dissecting how chemokines trigger lymphocyte integrins to support shear-resistant motility on and across cytokine-stimulated endothelial barriers, we found a critical role for high-affinity (HA) LFA-1 integrin in lymphocyte crawling on activated endothelium. Endothelial-presented chemokines triggered HA-LFA-1 and adhesive filopodia at numerous submicron dots scattered underneath crawling lymphocytes. Shear forces applied to endothelial-bound lymphocytes dramatically enhanced filopodia density underneath crawling lymphocytes. A fraction of the adhesive filopodia invaded the endothelial cells prior to and during TEM and extended large subluminal leading edge containing dots of HA-LFA-1 occupied by subluminal ICAM-1. Memory T cells generated more frequent invasive filopodia and transmigrated more rapidly than their naive counterparts. We propose that shear forces exerted on HA-LFA-1 trigger adhesive and invasive filopodia at apical endothelial surfaces and thereby promote lymphocyte crawling and probing for TEM sites.
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Both leukocytes and the endothelium become activated, causing upregulation of cell surface receptors mediating leukocyte-endothelial adhesion.
“Both leukocytes and the endothelium become activated, causing upregulation of cell surface receptors mediating leukocyte-endothelial adhesion (215, 216, 537).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [537]
The Discussion (page not available) describes chemokine-triggered activation of T-cell integrins and adhesion to cytokine-activated endothelial cells bearing ICAM-1 and VCAM-1. The Results (page not available) describe clustering of endothelial ICAM-1 beneath crawling T cells. These passages support activation and adhesion, but not the claim that activation of both cell types causes upregulation of cell-surface adhesion receptors. (LLM, conf=0.82)
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- Authors
- Shulman, Z., Shinder, V., Klein, E., Grabovsky, V., Yeger, O., Geron, E., Montresor, A., Bolomini-Vittori, M., Feigelson, S. W., Kirchhausen, T., Laudanna, C., Shakhar, G., & Alon, R.
- Affiliations
- Weizmann Institute of Science (IL)
- University of Verona (IT)
- Harvard University (US)
- Corresponding author
- Alon, Ronen
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 30
- Issue
- 3
- Pages
- 384-396
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2803105
- OpenAlex
- W2101026205
- Cited by
- 268
- References
- 1
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 11 · 2023: 13 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 15 · 2018: 19 · 2017: 14 · 2016: 21 · 2015: 20 · 2014: 18 · 2013: 17 · 2012: 21
- FWCI
- 20.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1635 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Goethe-Universität Frankfurt am Main
- Minerva Foundation
- Israel Science Foundation
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- LFA-1 integrin, lymphocyte transendothelial migration, shear force, ICAM-1, memory T cells, naive T cells, lymphocyte adhesion, endothelial barrier
- MeSH terms
- Cell Movement, Cells, Cultured, Endothelium, Vascular, Humans, T-Lymphocytes, Lymphocyte Function-Associated Antigen-1, Intercellular Adhesion Molecule-1, Chemokines
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