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| Status |
Public on Dec 05, 2006 |
| Title |
An inflammation-induced mechanism for leukocyte transmigration of lymphatic vessel endothelium. |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The exit of antigen-presenting cells (APC) and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels is however unknown. Here we show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LEC) leading to expression of the key leukocyte adhesion receptors ICAM-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 DC via afferent lymphatics. Lastly, we show that TNF_-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 mAbs. 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 anti-inflammatory therapy.
Keywords: TNFalpha, Lymphatic endothelium, induction, Inflammation
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| Overall design |
Global gene expression profile of normal dermal lymphatic endothelial cells cultured in media alone (no TNF) compared to that of normal dermal lymphatic endothelial cells stimulated with TNFalpha, 1 ng/ml for 48h.Triplicate biological samples were analyzed from human lymphatic endothelial cells (3 x controls; 3 x TNF treated) and a single sample analyzed from mouse lymphatic endothelial cells (1 x controls; 1 x TNF treated).
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| |
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| Contributor(s) |
Johnson L, Clasper S, Holt A, Lalor P, Baban D, Jackson DG |
| Citation(s) |
17116732 |
| |
| Submission date |
Nov 09, 2006 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Dilair Baban |
| E-mail(s) |
dilair.baban@well.ox.ac.uk
|
| Phone |
+44(0)1865287521
|
| Organization name |
University of Oxford
|
| Department |
Wellcome Trust Centre Human Genetics
|
| Lab |
Genomics
|
| Street address |
Roosevelt Drive
|
| City |
Oxford |
| ZIP/Postal code |
OX3 7BN |
| Country |
United Kingdom |
| |
|
| Platforms (2) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
|
| Samples (8)
|
| GSM143704 |
Mouse lymphatic endothelial cells Control |
| GSM143705 |
Mouse lymphatic endothelial cells TNFa treated |
| GSM143717 |
Human lymphatic endothelial cells Control_Rep 1 |
| GSM143898 |
Human lymphatic endothelial cells Control_Rep 2 |
| GSM143900 |
Human lymphatic endothelial cells Control_Rep 3 |
| GSM143907 |
Human lymphatic endothelial cells TNFalpha_Rep 1 |
| GSM143910 |
Human lymphatic endothelial cells TNFalpha_Rep 2 |
| GSM143914 |
Human lymphatic endothelial cells TNFalpha_Rep 3 |
|
| Relations |
| BioProject |
PRJNA100539 |
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