Rapid neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles.
Rapid neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles.
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DOI：
10.1093/cvr/cvac012
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发表时间：
2023-03-17
影响因子：
10.8
通讯作者：
中科院分区：
文献类型：
--
作者：
Acute myocardial infarction rapidly increases blood neutrophils (<2 h). Release from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 h after injury, and after neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 min) release of extracellular vesicles (EVs), which have emerged as an important means of cell–cell signalling and are thus a potential mechanism for communicating with remote tissues. Here, we show that injury to the myocardium rapidly mobilizes neutrophils from the spleen to peripheral blood and induces their transcriptional activation prior to arrival at the injured tissue. Time course analysis of plasma-EV composition revealed a rapid and selective increase in EVs bearing VCAM-1. These EVs, which were also enriched for miRNA-126, accumulated preferentially in the spleen where they induced local inflammatory gene and chemokine protein expression, and mobilized splenic-neutrophils to peripheral blood. Using CRISPR/Cas9 genome editing, we generated VCAM-1-deficient EC-EVs and showed that its deletion removed the ability of EC-EVs to provoke the mobilization of neutrophils. Furthermore, inhibition of miRNA-126 in vivo reduced myocardial infarction size in a mouse model. Our findings show a novel EV-dependent mechanism for the rapid mobilization of neutrophils to peripheral blood from a splenic reserve and establish a proof of concept for functional manipulation of EV-communications through genetic alteration of parent cells.
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脂肪组织 microRNA 作为人类肥胖中 CCL2 产生的调节因子。
影响因子：
7.7
作者：
Arner E;Mejhert N;Kulyté A;Balwierz PJ;Pachkov M;Cormont M;Lorente-Cebrián S;Ehrlund A;Laurencikiene J;Hedén P;Dahlman-Wright K;Tanti JF;Hayashizaki Y;Rydén M;Dahlman I;van Nimwegen E;Daub CO;Arner P
通讯作者：
Arner P
影响因子：
30.5
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Agudo, Judith;Ruzo, Albert;Tung, Navpreet;Salmon, Helene;Leboeuf, Marylene;Hashimoto, Daigo;Becker, Christian;Garrett-Sinha, Lee-Ann;Baccarini, Alessia;Merad, Miriam;Brown, Brian D.
通讯作者：
Brown, Brian D.
DOI：
10.1084/jem.20161621
发表时间：
2017-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Deniset JF;Surewaard BG;Lee WY;Kubes P
通讯作者：
Kubes P
影响因子：
20.3
作者：
Eash, Kyle J.;Means, Jacquelyn M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
2.8
作者：
Chia, Stanley;Nagurney, John T.;Jang, Ik-Kyung
通讯作者：
Jang, Ik-Kyung