Article ; Online: Fibroblast-type reticular stromal cells regulate the lymph node vasculature.
Journal of immunology (Baltimore, Md. : 1950)
2008 Volume 181, Issue 6, Page(s) 3887–3896
Abstract: The lymph node vasculature is essential to immune function, but mechanisms regulating lymph node vascular maintenance and growth are not well understood. Vascular endothelial growth factor (VEGF) is an important mediator of lymph node endothelial cell ... ...
| Abstract | The lymph node vasculature is essential to immune function, but mechanisms regulating lymph node vascular maintenance and growth are not well understood. Vascular endothelial growth factor (VEGF) is an important mediator of lymph node endothelial cell proliferation in stimulated lymph nodes. It is expressed basally in lymph nodes and up-regulated upon lymph node stimulation, but the identity of VEGF-expressing cells in lymph nodes is not known. We show that, at homeostasis, fibroblast-type reticular stromal cells (FRC) in the T zone and medullary cords are the principal VEGF-expressing cells in lymph nodes and that VEGF plays a role in maintaining endothelial cell proliferation, although peripheral node addressin (PNAd)(+) endothelial cells are less sensitive than PNAd(-) endothelial cells to VEGF blockade. Lymphotoxin beta receptor (LTbetaR) blockade reduces homeostatic VEGF levels and endothelial cell proliferation, and LTbetaR stimulation of murine fibroblast-type cells up-regulates VEGF expression, suggesting that LTbetaR signals on FRC regulate lymph node VEGF levels and, thereby, lymph node endothelial cell proliferation. At the initiation of immune responses, FRC remain the principal VEGF mRNA-expressing cells in lymph nodes, suggesting that FRC may play an important role in regulating vascular growth in stimulated nodes. In stimulated nodes, VEGF regulates the proliferation and expansion of both PNAd(+) and PNAd(-) endothelial cells. Taken together, these data suggest a role for FRC as paracrine regulators of lymph node endothelial cells and suggest that modulation of FRC VEGF expression may be a means to regulate lymph node vascularity and, potentially, immune function. |
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| MeSH term(s) | Animals ; Clone Cells ; Endothelium, Vascular/cytology ; Endothelium, Vascular/growth & development ; Endothelium, Vascular/immunology ; Fibroblasts/cytology ; Fibroblasts/immunology ; Genes, Reporter ; Homeostasis/immunology ; Lymph Nodes/blood supply ; Lymph Nodes/cytology ; Lymph Nodes/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mononuclear Phagocyte System/cytology ; Mononuclear Phagocyte System/growth & development ; Mononuclear Phagocyte System/immunology ; NIH 3T3 Cells ; Stromal Cells/cytology ; Stromal Cells/immunology ; Vascular Endothelial Growth Factor A/biosynthesis ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/physiology | ||||||||||
| Chemical Substances | Vascular Endothelial Growth Factor A | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2008-09-03 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 3056-9 | ||||||||||
| ISSN | 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381 | ||||||||||
| ISSN (online) | 1550-6606 | ||||||||||
| ISSN | 0022-1767 ; 1048-3233 ; 1047-7381 | ||||||||||
| DOI | 10.4049/jimmunol.181.6.3887 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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