Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death

Carlos Silvestre-Roig (), Quinte Braster, Kanin Wichapong, Ernest Y. Lee, Jean Marie Teulon, Nihel Berrebeh, Janine Winter, José M. Adrover, Giancarlo Santiago Santos, Alexander Froese, Patricia Lemnitzer, Almudena Ortega-Gómez, Raphael Chevre, Julian Marschner, Ariane Schumski, Carla Winter, Laura Perez-Olivares, Chang Pan, Nicole Paulin, Tom Schoufour, Helene Hartwig, Silvia González-Ramos, Frits Kamp, Remco T. A. Megens, Kerri A. Mowen, Matthias Gunzer, Lars Maegdefessel, Tilman Hackeng, Esther Lutgens, Mat Daemen, Julia Blume, Hans-Joachim Anders, Viacheslav O. Nikolaev, Jean-Luc Pellequer, Christian Weber, Andrés Hidalgo, Gerry A. F. Nicolaes, Gerard C. L. Wong and Oliver Soehnlein ()
Additional contact information
Carlos Silvestre-Roig: Institute for Cardiovascular Prevention (IPEK), LMU München
Quinte Braster: Institute for Cardiovascular Prevention (IPEK), LMU München
Kanin Wichapong: CARIM, University Maastricht
Ernest Y. Lee: University of California, Los Angeles
Jean Marie Teulon: Université Grenoble Alpes, CEA, CNRS, IBS
Nihel Berrebeh: Université Grenoble Alpes, CEA, CNRS, IBS
Janine Winter: Institute for Cardiovascular Prevention (IPEK), LMU München
José M. Adrover: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
Giancarlo Santiago Santos: University of California, Los Angeles
Alexander Froese: University Medical Center Hamburg-Eppendorf
Patricia Lemnitzer: Institute for Cardiovascular Prevention (IPEK), LMU München
Almudena Ortega-Gómez: Institute for Cardiovascular Prevention (IPEK), LMU München
Raphael Chevre: Institute for Cardiovascular Prevention (IPEK), LMU München
Julian Marschner: LMU München
Ariane Schumski: Institute for Cardiovascular Prevention (IPEK), LMU München
Carla Winter: Institute for Cardiovascular Prevention (IPEK), LMU München
Laura Perez-Olivares: Institute for Cardiovascular Prevention (IPEK), LMU München
Chang Pan: Institute for Cardiovascular Prevention (IPEK), LMU München
Nicole Paulin: Institute for Cardiovascular Prevention (IPEK), LMU München
Tom Schoufour: AMC
Helene Hartwig: Institute for Cardiovascular Prevention (IPEK), LMU München
Silvia González-Ramos: Institute for Cardiovascular Prevention (IPEK), LMU München
Frits Kamp: BMC, Metabolic Biochemistry, LMU München
Remco T. A. Megens: Institute for Cardiovascular Prevention (IPEK), LMU München
Kerri A. Mowen: The Scripps Research Institute
Matthias Gunzer: University Hospital Essen
Lars Maegdefessel: Partner Site Munich Heart Alliance
Tilman Hackeng: CARIM, University Maastricht
Esther Lutgens: Institute for Cardiovascular Prevention (IPEK), LMU München
Mat Daemen: AMC
Julia Blume: Max Planck Institute of Biochemistry
Hans-Joachim Anders: LMU München
Viacheslav O. Nikolaev: University Medical Center Hamburg-Eppendorf
Jean-Luc Pellequer: Université Grenoble Alpes, CEA, CNRS, IBS
Christian Weber: Institute for Cardiovascular Prevention (IPEK), LMU München
Andrés Hidalgo: Institute for Cardiovascular Prevention (IPEK), LMU München
Gerry A. F. Nicolaes: CARIM, University Maastricht
Gerard C. L. Wong: University of California, Los Angeles
Oliver Soehnlein: Institute for Cardiovascular Prevention (IPEK), LMU München

Nature, 2019, vol. 569, issue 7755, 236-240

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1167-6 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:569:y:2019:i:7755:d:10.1038_s41586-019-1167-6

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-1167-6

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().