Imperial College London
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DrSanoojSoni

Faculty of Medicine, Department of Surgery & Cancer

Clinical Senior Lecturer in Critical and Perioperative Care
 
 
 
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Contact

 

s.soni

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Soni:2019:10.1096/fj.201802386R,
author = {Soni, S and O'Dea, K and Tan, YY and Cho, K and Abe, E and Romano, R and Cui, J and Ma, D and Sarathchandra, P and Wilson, MR and Takata, M},
doi = {10.1096/fj.201802386R},
journal = {FASEB Journal},
title = {ATP redirects cytokine trafficking and promotes novel membrane TNF signalling via microvesicles},
url = {http://dx.doi.org/10.1096/fj.201802386R},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cellular stress or injury induces release of endogenous danger signals such as ATP, which plays a central role in activating immune cells. ATP is essential for the release of nonclassically secreted cytokines such as IL-1β but, paradoxically, has been reported to inhibit the release of classically secreted cytokines such as TNF. Here, we reveal that ATP does switch off soluble TNF (17 kDa) release from LPS-treated macrophages, but rather than inhibiting the entire TNF secretion, ATP packages membrane TNF (26 kDa) within microvesicles (MVs). Secretion of membrane TNF within MVs bypasses the conventional endoplasmic reticulum– and Golgi transport–dependent pathway and is mediated by acid sphingomyelinase. These membrane TNF–carrying MVs are biologically more potent than soluble TNF in vivo, producing significant lung inflammation in mice. Thus, ATP critically alters TNF trafficking and secretion from macrophages, inducing novel unconventional membrane TNF signaling via MVs without direct cell-to-cell contact. These data have crucial implications for this key cytokine, particularly when therapeutically targeting TNF in acute inflammatory diseases.—Soni, S., O’Dea, K. P., Tan, Y. Y., Cho, K., Abe, E., Romano, R., Cui, J., Ma, D., Sarathchandra, P., Wilson, M. R., Takata, M. ATP redirects cytokine trafficking and promotes novel membrane TNF signaling via microvesicles.
AU  - Soni,S
AU  - O'Dea,K
AU  - Tan,YY
AU  - Cho,K
AU  - Abe,E
AU  - Romano,R
AU  - Cui,J
AU  - Ma,D
AU  - Sarathchandra,P
AU  - Wilson,MR
AU  - Takata,M
DO  - 10.1096/fj.201802386R
PY  - 2019///
SN  - 0892-6638
TI  - ATP redirects cytokine trafficking and promotes novel membrane TNF signalling via microvesicles
T2  - FASEB Journal
UR  - http://dx.doi.org/10.1096/fj.201802386R
ER  -
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