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ATP redirects cytokine trafficking and promotes novel membrane TNF signaling via microvesicles
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 s...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Federation of American Societies for Experimental Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463909/ https://www.ncbi.nlm.nih.gov/pubmed/30776316 http://dx.doi.org/10.1096/fj.201802386R |
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author | Soni, Sanooj O’Dea, Kieran P. Tan, Ying Ying Cho, Kahori Abe, Eiko Romano, Rosalba Cui, Jiang Ma, Daqing Sarathchandra, Padmini Wilson, Michael R. Takata, Masao |
author_facet | Soni, Sanooj O’Dea, Kieran P. Tan, Ying Ying Cho, Kahori Abe, Eiko Romano, Rosalba Cui, Jiang Ma, Daqing Sarathchandra, Padmini Wilson, Michael R. Takata, Masao |
author_sort | Soni, Sanooj |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6463909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Federation of American Societies for Experimental Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-64639092019-04-18 ATP redirects cytokine trafficking and promotes novel membrane TNF signaling via microvesicles Soni, Sanooj O’Dea, Kieran P. Tan, Ying Ying Cho, Kahori Abe, Eiko Romano, Rosalba Cui, Jiang Ma, Daqing Sarathchandra, Padmini Wilson, Michael R. Takata, Masao FASEB J Research 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. Federation of American Societies for Experimental Biology 2019-05 2019-02-18 /pmc/articles/PMC6463909/ /pubmed/30776316 http://dx.doi.org/10.1096/fj.201802386R Text en © The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Soni, Sanooj O’Dea, Kieran P. Tan, Ying Ying Cho, Kahori Abe, Eiko Romano, Rosalba Cui, Jiang Ma, Daqing Sarathchandra, Padmini Wilson, Michael R. Takata, Masao ATP redirects cytokine trafficking and promotes novel membrane TNF signaling via microvesicles |
title | ATP redirects cytokine trafficking and promotes novel membrane TNF signaling via microvesicles |
title_full | ATP redirects cytokine trafficking and promotes novel membrane TNF signaling via microvesicles |
title_fullStr | ATP redirects cytokine trafficking and promotes novel membrane TNF signaling via microvesicles |
title_full_unstemmed | ATP redirects cytokine trafficking and promotes novel membrane TNF signaling via microvesicles |
title_short | ATP redirects cytokine trafficking and promotes novel membrane TNF signaling via microvesicles |
title_sort | atp redirects cytokine trafficking and promotes novel membrane tnf signaling via microvesicles |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463909/ https://www.ncbi.nlm.nih.gov/pubmed/30776316 http://dx.doi.org/10.1096/fj.201802386R |
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