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Cited by 141Lymphatic System and DiseasesLymphatic Disorders and TreatmentsBarrier Structure and Function Studies

The effects of inflammatory cytokines on lymphatic endothelial barrier function

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Cromer, Walter E., Zawieja, Scott D., Tharakan, Binu, Childs, Ed W., Newell, M. Karen, Zawieja, David C.·2014·Angiogenesis
DOI 10.1007/s10456-013-9393-2PMC PMC4314095
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Abstract

Proper lymphatic function is necessary for the transport of fluids, macromolecules, antigens and immune cells out of the interstitium. The lymphatic endothelium plays important roles in the modulation of lymphatic contractile activity and lymph transport, but it's role as a barrier between the lymph and interstitial compartments is less well understood. Alterations in lymphatic function have long been associated with edema and inflammation although the integrity of the lymphatic endothelial barrier during inflammation is not well-defined. In this paper we evaluated the integrity of the lymphatic barrier in response to inflammatory stimuli commonly associated with increased blood endothelial permeability. We utilized in vitro assays of lymphatic endothelial cell (LEC) monolayer barrier function after treatment with different inflammatory cytokines and signaling molecules including TNF-α, IL-6, IL-1β, IFN-γ and LPS. Moderate increases in an index of monolayer barrier dysfunction were noted with all treatments (20-60 % increase) except IFN-γ which caused a greater than 2.5-fold increase. Cytokine-induced barrier dysfunction was blocked or reduced by the addition of LNAME, except for IL-1β and LPS treatments, suggesting a regulatory role for nitric oxide. The decreased LEC barrier was associated with modulation of both intercellular adhesion and intracellular cytoskeletal activation. Cytokine treatments reduced the expression of VE-cadherin and increased scavenging of β-catenin in the LECs and this was partially reversed by LNAME. Likewise the phosphorylation of myosin light chain 20 at the regulatory serine 19 site, which accompanied the elevated monolayer barrier dysfunction in response to cytokine treatment, was also blunted by LNAME application. This suggests that the lymphatic barrier is regulated during inflammation and that certain inflammatory signals may induce large increases in permeability.

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  • Lymphatic permeability rises significantly in response to inflammatory cytokines.

    “As with BECs, lymphatic permeability rises significantly in response to inflammatory cytokines (36).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [36]

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Authors
Cromer, W. E., Zawieja, S. D., Tharakan, B., Childs, E. W., Newell, M. K., & Zawieja, D. C.
Affiliations
  • Texas A&M Health Science Center (US)
  • Texas A&M University (US)
  • Morehouse School of Medicine (US)
Corresponding author
Cromer, Walter E.
ORCID
Venue
Angiogenesis
Publisher
Springer Science and Business Media LLC
Published
2013-10-20
Volume
17
Issue
2
Pages
395-406
ISSN
  • 0969-6970 (ISSN-L)
  • 1573-7209
DOI
10.1007/s10456-013-9393-2
PMC
PMC4314095
OpenAlex
W2026605197
Cited by
141
References
2
Citations by year
2026: 16 · 2025: 13 · 2024: 5 · 2023: 15 · 2022: 12 · 2021: 9 · 2020: 17 · 2019: 7 · 2018: 9 · 2017: 10 · 2016: 8 · 2015: 14 · 2014: 6
FWCI
4.37
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Angiogenesis (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL070308, HL 094269, HL070308, R21HL085659, R01HL075199, R01HL094269)
  • National Cancer Institute (R01CA140732, CA140732)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK099221, R01DK099221)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
inflammatory cytokines, lymphatic endothelial cells, endothelial permeability, TNF-α, interleukin-6, IL-1β, interferon-gamma, lipopolysaccharide, nitric oxide, L-NAME, VE-cadherin, β-catenin, cell-cell adhesion, lymphatic function, inflammation
MeSH terms
Cadherin 5, Animals, Cell Membrane Permeability, Endothelium, Vascular, Fluorescent Antibody Technique, Blotting, Western, Antigens, CD, Cadherins, Cytokines, Rats, Sprague-Dawley, Proliferating Cell Nuclear Antigen, Inflammation Mediators, S-Nitroso-N-Acetylpenicillamine, Vesicular Transport Proteins, Endothelial Cells, Cell Proliferation

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