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Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death

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Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death. / Silvestre-Roig, Carlos; Braster, Quinte; Wichapong, Kanin; Lee, Ernest Y; Teulon, Jean Marie; Berrebeh, Nihel; Winter, Janine; Adrover, José M; Santos, Giancarlo Santiago; Froese, Alexander; Lemnitzer, Patricia; Ortega-Gómez, Almudena; Chevre, Raphael; Marschner, Julian; Schumski, Ariane; Winter, Carla; Perez-Olivares, Laura; Pan, Chang; Paulin, Nicole; Schoufour, Tom; Hartwig, Helene; González-Ramos, Silvia; Kamp, Frits; Megens, Remco T A; Mowen, Kerri A; Gunzer, Matthias; Maegdefessel, Lars; Hackeng, Tilman; Lutgens, Esther; Daemen, Mat; von Blume, Julia; Anders, Hans-Joachim; Nikolaev, Viacheslav O; Pellequer, Jean-Luc; Weber, Christian; Hidalgo, Andrés; Nicolaes, Gerry A F; Wong, Gerard C L; Soehnlein, Oliver.

In: NATURE, Vol. 569, No. 7755, 05.2019, p. 236-240.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Silvestre-Roig, C, Braster, Q, Wichapong, K, Lee, EY, Teulon, JM, Berrebeh, N, Winter, J, Adrover, JM, Santos, GS, Froese, A, Lemnitzer, P, Ortega-Gómez, A, Chevre, R, Marschner, J, Schumski, A, Winter, C, Perez-Olivares, L, Pan, C, Paulin, N, Schoufour, T, Hartwig, H, González-Ramos, S, Kamp, F, Megens, RTA, Mowen, KA, Gunzer, M, Maegdefessel, L, Hackeng, T, Lutgens, E, Daemen, M, von Blume, J, Anders, H-J, Nikolaev, VO, Pellequer, J-L, Weber, C, Hidalgo, A, Nicolaes, GAF, Wong, GCL & Soehnlein, O 2019, 'Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death', NATURE, vol. 569, no. 7755, pp. 236-240. https://doi.org/10.1038/s41586-019-1167-6

APA

Silvestre-Roig, C., Braster, Q., Wichapong, K., Lee, E. Y., Teulon, J. M., Berrebeh, N., Winter, J., Adrover, J. M., Santos, G. S., Froese, A., Lemnitzer, P., Ortega-Gómez, A., Chevre, R., Marschner, J., Schumski, A., Winter, C., Perez-Olivares, L., Pan, C., Paulin, N., ... Soehnlein, O. (2019). Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death. NATURE, 569(7755), 236-240. https://doi.org/10.1038/s41586-019-1167-6

Vancouver

Silvestre-Roig C, Braster Q, Wichapong K, Lee EY, Teulon JM, Berrebeh N et al. Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death. NATURE. 2019 May;569(7755):236-240. https://doi.org/10.1038/s41586-019-1167-6

Bibtex

@article{168e6fa5027343e08f6d78b23e83cd5c,
title = "Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death",
abstract = "The perpetuation of inflammation is an important pathophysiological contributor to the global medical burden. Chronic inflammation is promoted by non-programmed cell death1,2; however, how inflammation is instigated, its cellular and molecular mediators, and its therapeutic value are poorly defined. Here we use mouse models of atherosclerosis-a major underlying cause of mortality worldwide-to demonstrate that extracellular histone H4-mediated membrane lysis of smooth muscle cells (SMCs) triggers arterial tissue damage and inflammation. We show that activated lesional SMCs attract neutrophils, triggering the ejection of neutrophil extracellular traps that contain nuclear proteins. Among them, histone H4 binds to and lyses SMCs, leading to the destabilization of plaques; conversely, the neutralization of histone H4 prevents cell death of SMCs and stabilizes atherosclerotic lesions. Our data identify a form of cell death found at the core of chronic vascular disease that is instigated by leukocytes and can be targeted therapeutically.",
keywords = "Animals, Arteries/pathology, Atherosclerosis/pathology, Cell Death, Cell Membrane/drug effects, Disease Models, Animal, Female, Histones/antagonists & inhibitors, Inflammation/metabolism, Mice, Mice, Inbred C57BL, Myocytes, Smooth Muscle/pathology, Neutrophils/cytology, Porosity, Protein Binding/drug effects",
author = "Carlos Silvestre-Roig and Quinte Braster and Kanin Wichapong and Lee, {Ernest Y} and Teulon, {Jean Marie} and Nihel Berrebeh and Janine Winter and Adrover, {Jos{\'e} M} and Santos, {Giancarlo Santiago} and Alexander Froese and Patricia Lemnitzer and Almudena Ortega-G{\'o}mez and Raphael Chevre and Julian Marschner and Ariane Schumski and Carla Winter and Laura Perez-Olivares and Chang Pan and Nicole Paulin and Tom Schoufour and Helene Hartwig and Silvia Gonz{\'a}lez-Ramos and Frits Kamp and Megens, {Remco T A} and Mowen, {Kerri A} and Matthias Gunzer and Lars Maegdefessel and Tilman Hackeng and Esther Lutgens and Mat Daemen and {von Blume}, Julia and Hans-Joachim Anders and Nikolaev, {Viacheslav O} and Jean-Luc Pellequer and Christian Weber and Andr{\'e}s Hidalgo and Nicolaes, {Gerry A F} and Wong, {Gerard C L} and Oliver Soehnlein",
year = "2019",
month = may,
doi = "10.1038/s41586-019-1167-6",
language = "English",
volume = "569",
pages = "236--240",
journal = "NATURE",
issn = "0028-0836",
publisher = "NATURE PUBLISHING GROUP",
number = "7755",

}

RIS

TY - JOUR

T1 - Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death

AU - Silvestre-Roig, Carlos

AU - Braster, Quinte

AU - Wichapong, Kanin

AU - Lee, Ernest Y

AU - Teulon, Jean Marie

AU - Berrebeh, Nihel

AU - Winter, Janine

AU - Adrover, José M

AU - Santos, Giancarlo Santiago

AU - Froese, Alexander

AU - Lemnitzer, Patricia

AU - Ortega-Gómez, Almudena

AU - Chevre, Raphael

AU - Marschner, Julian

AU - Schumski, Ariane

AU - Winter, Carla

AU - Perez-Olivares, Laura

AU - Pan, Chang

AU - Paulin, Nicole

AU - Schoufour, Tom

AU - Hartwig, Helene

AU - González-Ramos, Silvia

AU - Kamp, Frits

AU - Megens, Remco T A

AU - Mowen, Kerri A

AU - Gunzer, Matthias

AU - Maegdefessel, Lars

AU - Hackeng, Tilman

AU - Lutgens, Esther

AU - Daemen, Mat

AU - von Blume, Julia

AU - Anders, Hans-Joachim

AU - Nikolaev, Viacheslav O

AU - Pellequer, Jean-Luc

AU - Weber, Christian

AU - Hidalgo, Andrés

AU - Nicolaes, Gerry A F

AU - Wong, Gerard C L

AU - Soehnlein, Oliver

PY - 2019/5

Y1 - 2019/5

N2 - The perpetuation of inflammation is an important pathophysiological contributor to the global medical burden. Chronic inflammation is promoted by non-programmed cell death1,2; however, how inflammation is instigated, its cellular and molecular mediators, and its therapeutic value are poorly defined. Here we use mouse models of atherosclerosis-a major underlying cause of mortality worldwide-to demonstrate that extracellular histone H4-mediated membrane lysis of smooth muscle cells (SMCs) triggers arterial tissue damage and inflammation. We show that activated lesional SMCs attract neutrophils, triggering the ejection of neutrophil extracellular traps that contain nuclear proteins. Among them, histone H4 binds to and lyses SMCs, leading to the destabilization of plaques; conversely, the neutralization of histone H4 prevents cell death of SMCs and stabilizes atherosclerotic lesions. Our data identify a form of cell death found at the core of chronic vascular disease that is instigated by leukocytes and can be targeted therapeutically.

AB - The perpetuation of inflammation is an important pathophysiological contributor to the global medical burden. Chronic inflammation is promoted by non-programmed cell death1,2; however, how inflammation is instigated, its cellular and molecular mediators, and its therapeutic value are poorly defined. Here we use mouse models of atherosclerosis-a major underlying cause of mortality worldwide-to demonstrate that extracellular histone H4-mediated membrane lysis of smooth muscle cells (SMCs) triggers arterial tissue damage and inflammation. We show that activated lesional SMCs attract neutrophils, triggering the ejection of neutrophil extracellular traps that contain nuclear proteins. Among them, histone H4 binds to and lyses SMCs, leading to the destabilization of plaques; conversely, the neutralization of histone H4 prevents cell death of SMCs and stabilizes atherosclerotic lesions. Our data identify a form of cell death found at the core of chronic vascular disease that is instigated by leukocytes and can be targeted therapeutically.

KW - Animals

KW - Arteries/pathology

KW - Atherosclerosis/pathology

KW - Cell Death

KW - Cell Membrane/drug effects

KW - Disease Models, Animal

KW - Female

KW - Histones/antagonists & inhibitors

KW - Inflammation/metabolism

KW - Mice

KW - Mice, Inbred C57BL

KW - Myocytes, Smooth Muscle/pathology

KW - Neutrophils/cytology

KW - Porosity

KW - Protein Binding/drug effects

U2 - 10.1038/s41586-019-1167-6

DO - 10.1038/s41586-019-1167-6

M3 - SCORING: Journal article

C2 - 31043745

VL - 569

SP - 236

EP - 240

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7755

ER -