Imperial College London
Alternate

Emeritus ProfessorTimothyWilliams

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor in Airway Disease
 
 
 
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Contact

 

+44 (0)20 7594 3159tim.williams Website

 
 
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Location

 

Office no. 360Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Finsterbusch:2014:10.1084/jem.20132413,
author = {Finsterbusch, M and Voisin, M-B and Beyrau, M and Williams, TJ and Nourshargh, S},
doi = {10.1084/jem.20132413},
journal = {Journal of Experimental Medicine},
pages = {1306--1313},
title = {Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF},
url = {http://dx.doi.org/10.1084/jem.20132413},
volume = {211},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Microvascular plasma protein leakage is an essential component of the inflammatoryresponse and serves an important function in local host defense and tissue repair. Mediatorssuch as histamine and bradykinin act directly on venules to increase the permeabilityof endothelial cell (EC) junctions. Neutrophil chemoattractants also induce leakage, aresponse that is dependent on neutrophil adhesion to ECs, but the underlying mechanismhas proved elusive. Through application of confocal intravital microscopy to the mousecremaster muscle, we show that neutrophils responding to chemoattractants release TNFwhen in close proximity of EC junctions. In vitro, neutrophils adherent to ICAM-1 or ICAM-2rapidly released TNF in response to LTB4, C5a, and KC. Further, in TNFR/ mice, neutrophilsaccumulated normally in response to chemoattractants administered to the cremastermuscle or dorsal skin, but neutrophil-dependent plasma protein leakage was abolished.Similar results were obtained in chimeric mice deficient in leukocyte TNF. A locally injectedTNF blocking antibody was also able to inhibit neutrophil-dependent plasma leakage, buthad no effect on the response induced by bradykinin. The results suggest that TNF mediatesneutrophil-dependent microvascular leakage. This mechanism may contribute to the effectsof TNF inhibitors in inflammatory diseases and indicates possible applications in lifethreateningacute edema.
AU  - Finsterbusch,M
AU  - Voisin,M-B
AU  - Beyrau,M
AU  - Williams,TJ
AU  - Nourshargh,S
DO  - 10.1084/jem.20132413
EP  - 1313
PY  - 2014///
SN  - 1540-9538
SP  - 1306
TI  - Neutrophils recruited by chemoattractants in vivo induce microvascular plasma protein leakage through secretion of TNF
T2  - Journal of Experimental Medicine
UR  - http://dx.doi.org/10.1084/jem.20132413
UR  - http://hdl.handle.net/10044/1/28221
VL  - 211
ER  -
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