Cited by 346Lymphatic System and DiseasesCell Adhesion Molecules ResearchLymphatic Disorders and Treatments

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An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium

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Johnson, Louise A., Clasper, Steven, Holt, Andrew P., Lalor, Patricia F., Baban, Dilair, Jackson, David G.·2006·The Journal of Experimental Medicine

DOI 10.1084/jem.20051759PMC PMC2118156

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Abstract

The exit of antigen-presenting cells and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such an exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels are unknown. We show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LECs), leading to expression of the key leukocyte adhesion receptors intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, as well as a discrete panel of chemokines and other potential regulators of leukocyte transmigration. Furthermore, we show that both ICAM-1 and VCAM-1 are induced in the dermal lymphatic vessels of mice exposed to skin contact hypersensitivity where they mediate lymph node trafficking of dendritic cells (DCs) via afferent lymphatics. Lastly, we show that tumor necrosis factor α stimulates both DC adhesion and transmigration of dermal LEC monolayers in vitro and that the process is efficiently inhibited by ICAM-1 and VCAM-1 adhesion-blocking monoclonal antibodies. These results reveal a CAM-mediated mechanism for recruiting leukocytes to the lymph nodes in inflammation and highlight the process of lymphatic transmigration as a potential new target for antiinflammatory therapy.

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Authors: Johnson, L. A., Clasper, S., Holt, A. P., Lalor, P. F., Baban, D., & Jackson, D. G.
Affiliations: John Radcliffe Hospital (GB)
University of Birmingham (GB)
University of Oxford (GB)
ORCID: Johnson, Louise A.
Lalor, Patricia F.
Jackson, David G.
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2006-11-20
Volume: 203
Issue: 12
Pages: 2763-2777
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.20051759
PMC: PMC2118156
OpenAlex: W2163380226
Cited by: 346
References: 63
Citations by year: 2026: 12 · 2025: 7 · 2024: 14 · 2023: 17 · 2022: 16 · 2021: 20 · 2020: 19 · 2019: 12 · 2018: 17 · 2017: 17 · 2016: 24 · 2015: 14 · 2014: 20 · 2013: 28 · 2012: 16
FWCI: 9.04
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders: Cancer Research UK
Medical Research Council
Topics: Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
Keywords: leukocyte transmigration, lymphatic endothelium, dermal lymphatic vessels, ICAM-1, VCAM-1, E-selectin, chemokines, dendritic cells, lymph node trafficking, afferent lymphatics, TNF-α, inflammatory cytokines, leukocyte adhesion
MeSH terms: Adult, Animals, Cells, Cultured, Dermatitis, Contact, Endothelium, Lymphatic, Humans, Leukocytes, Male, Mice, Inbred BALB C, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Lymphatic Vessels, Mice

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An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium

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