HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4
- Authors
- Tadie, Jean-Marc; Bae, Hong-Beom; Jiang, Shaoning; Park, Dae Won; Bell, Celeste P.; Yang, Huan; Pittet, Jean-Francois; Tracey, Kevin; Thannickal, Victor J.; Abraham, Edward; Zmijewski, Jaroslaw W.
- Issue Date
- 3월-2013
- Publisher
- AMER PHYSIOLOGICAL SOC
- Keywords
- inflammation; lipopolysaccharide
- Citation
- AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v.304, no.5, pp.L342 - L349
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
- Volume
- 304
- Number
- 5
- Start Page
- L342
- End Page
- L349
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/103909
- DOI
- 10.1152/ajplung.00151.2012
- ISSN
- 1040-0605
- Abstract
- Tadie J-M, Bae H-B, Jiang S, Park DW, Bell CP, Yang H, Pittet J-F, Tracey K, Thannickal VJ, Abraham E, Zmijewski JW. HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. Am J Physiol Lung Cell Mol Physiol 304: L342-L349, 2013. First published January 11, 2013; doi:10.1152/ajplung.00151.2012.-Although neutrophil extracellular traps (NETs) form to prevent dissemination of pathogenic microorganisms, excessive release of DNA and DNA-associated proteins can also perpetuate sterile inflammation. In this study, we found that the danger-associated molecular pattern protein high-mobility group box 1 (HMGB1) can induce NET formation. NET formation was found after exposure of wild-type and receptor for advanced glycation end products-deficient neutrophil to HMGB1, whereas deficiency of Toll-like receptor (TLR)4 diminished the ability of neutrophils to produce NETs. Incubation of neutrophils with HMGB1 significantly increased the amount of DNA and histone 3 released as well as intracellular histone 3 citrullination, a signaling event that precedes chromatin decondensation. In vivo, neutrophils isolated from bronchoalveolar lavages of mice exposed to LPS and HMGB1 showed consistently greater ability to produce NETs compared with pulmonary neutrophils from mice that received LPS alone. In contrast, mice treated with LPS and neutralizing antibody to HMGB1 had decreased amounts of the inflammatory cytokines TNF-alpha and macrophage inflammatory protein 2, as well as of free DNA and histone 3 in bronchoalveolar lavage fluids. Airway neutrophils from LPS-exposed mice that had been treated with anti-HMGB1 antibodies showed decreased citrullination of histone 3. These results demonstrate that interactions between HMGB1 and TLR4 enhance the formation of NETs and provide a novel mechanism through which HMGB1 may contribute to the severity of neutrophil-associated inflammatory conditions.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.