Monocytes Induce Reversible Focal Changes in Vascular Endothelial Cadherin Complex during Transendothelial Migration under Flow
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The vascular endothelial cell cadherin complex (VE-cadherin, alpha-, beta-, and gamma-catenin, and p120/p100) localizes to adherens junctions surrounding vascular endothelial cells and may play a critical role in the transendothelial migration of circulating blood leukocytes. Previously, we have reported that neutrophil adhesion to human umbilical vein endothelial cell (HUVEC) monolayers, under static conditions, results in a dramatic loss of the VE-cadherin complex. Subsequent studies by us and others (Moll, T., E. Dejana, and D. Vestweber. 1998. J. Cell Biol. 140:403-407) suggested that this phenomenon might reflect degradation by neutrophil proteases released during specimen preparation. We postulated that some form of disruption of the VE-cadherin complex might, nonetheless, be a physiological process during leukocyte transmigration. In the present study, the findings demonstrate a specific, localized effect of migrating leukocytes on the VE-cadherin complex in cytokine-activated HUVEC monolayers. Monocytes and in vitro differentiated U937 cells induce focal loss in the staining of VE-cadherin, alpha-catenin, beta-catenin, and plakoglobin during transendothelial migration under physiological flow conditions. These events are inhibited by antibodies that prevent transendothelial migration and are reversed following transmigration. Together, these data suggest that an endothelial-dependent step of transient and focal disruption of the VE-cadherin complex occurs during leukocyte transmigration.
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Adherens junctions regulate transendothelial migration of lymphocytes, monocytes, and neutrophils.
“AJs are connected to cytoskeleton, modulate receptor signaling (203), and regulate transendothelial migration of lymphocytes (601), monocytes (12, 203), and neutrophils (642).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [12]
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Self-citationNovel regulators of endothelial barrier function
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Mechanical Forces Induced by the Transendothelial Migration of Human Neutrophils
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Self-citationNovel chemokine functions in lymphocyte migration through vascular endothelium under shear flow
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Self-citationProteinase 3 Contributes to Transendothelial Migration of NB1-Positive Neutrophils
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Self-citationVE-cadherin-induced Cdc42 Signaling Regulates Formation of Membrane Protrusions in Endothelial Cells
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SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration
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Self-citationCCR3-Active Chemokines Promote Rapid Detachment of Eosinophils from VCAM-1 In Vitro
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- Authors
- Allport, J. R., Muller, W. A., & Luscinskas, F. W.
- Affiliations
- Brigham and Women's Hospital (US)
- bDepartment of Pathology, Weill Medical College of Cornell University, New York, New York 10021
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2000-01-10
- Volume
- 148
- Issue
- 1
- Pages
- 203-216
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2156206
- OpenAlex
- W2027826658
- Cited by
- 199
- References
- 45
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 6 · 2014: 8 · 2013: 7 · 2012: 6
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL046849, HL-53993, HL 46849, P01HL036028, HL36028, R01HL053993)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- VE-cadherin, adherens junctions, monocytes, leukocyte transendothelial migration, alpha-catenin, β-catenin, plakoglobin, human umbilical vein endothelial cells, U937 cells, endothelial cell adhesion
- MeSH terms
- Cadherin 5, Cell Movement, Cells, Cultured, Cytoskeletal Proteins, Endothelium, Vascular, Humans, Monocytes, Staining and Labeling, Trans-Activators, Antigens, CD, Cadherins, Lipopolysaccharide Receptors, Platelet Endothelial Cell Adhesion Molecule-1, U937 Cells, beta Catenin, alpha Catenin
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