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PMID: 17625067 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

VEGF-A produced by chronically inflamed tissue induces lymphangiogenesis in draining lymph nodes.

Blood ·Vol. 110 ·No. 9 ·2007-11-01 ·Pages 3158-67

Halin C, Tobler NE, Vigl B, Brown LF, Detmar M

Abstract

Lymphangiogenesis is involved in tumor cell metastasis and plays a major role in chronic inflammatory disorders. To investigate the role of lymphangiogenesis in inflammation, we induced and maintained delayed-type hypersensitivity (DTH) reactions in the ears of mice and then analyzed the resulting lymphangiogenesis in the inflamed tissue and draining lymph nodes (LNs) by quantitative fluorescence-activated cell sorting (FACS) and by immunofluorescence. Long-lasting inflammation induced a significant increase in the number of lymphatic endothelial cells, not only in the inflamed ears but also in the ear-draining auricular LNs. Inflammation-induced lymphangiogenesis was potently blocked by systemic administration of a vascular endothelial growth factor (VEGF)-A neutralizing antibody. Surprisingly, tissue inflammation specifically induced LN lymphangiogenesis but not LN angiogenesis. These findings were explained by analysis of both VEGF-A protein and mRNA levels, which revealed that VEGF-A was expressed at high mRNA and protein levels in inflamed ears but that expression was increased only at the protein level in activated LNs. Inflammation-induced lymphangiogenesis in LNs was independent of the presence of nodal B lymphocytes, as shown in B cell-deficient mice. Our data reveal that chronic inflammation actively induces lymphangiogenesis in LNs, which is controlled remotely, by lymphangiogenic factors produced at the site of inflammation.

MeSH Terms
Animals Chronic Disease Dermatitis, Allergic Contact/pathology Endothelial Cells/pathology Female Inflammation/genetics,metabolism,pathology Lymph Nodes/metabolism,pathology Lymphangiogenesis/genetics Mice Mice, Inbred C57BL Mice, SCID Mice, Transgenic Skin/pathology Vascular Endothelial Growth Factor A/genetics,metabolism,physiology
Chemicals
Vascular Endothelial Growth Factor A vascular endothelial growth factor A, mouse
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Halin Cornelia
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Tobler Nadja E
Vigl Benjamin
Brown Lawrence F
Detmar Michael
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2007-01-066811
Published
2007-11-01
Epub
2007-00-11
Pages
3158-67
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2200913
Subset
IM
Grants
NCI NIH HHS · P01 CA092644 · United States
NCI NIH HHS · R01 CA069184 · United States
NCI NIH HHS · CA 69184 · United States
NCI NIH HHS · CA 92644 · United States
External Links
PubMed source DOI: 10.1182/blood-2007-01-066811 PMC Full Text View journal details
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