HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4

Jean Marc Tadie, Hong Beom Bae, Shaoning Jiang, Dae Won Park, Celeste P. Bell, Huan Yang, Jean Francois Pittet, Kevin Tracey, Victor J. Thannickal, Edward Abraham, Jaroslaw W. Zmijewski

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

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-α 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume304
Issue number5
DOIs
Publication statusPublished - 2013 Mar 11

Fingerprint

Toll-Like Receptor 4
Neutrophils
Histones
DNA
Chemokine CXCL2
HMGB1 Protein
Bronchoalveolar Lavage Fluid
Bronchoalveolar Lavage
Extracellular Traps
Neutralizing Antibodies
Chromatin
Cytokines
Inflammation
Lung
Antibodies

Keywords

  • Inflammation
  • Lipopolysaccharide

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. / 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.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 304, No. 5, 11.03.2013.

Research output: Contribution to journalArticle

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. / HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2013 ; Vol. 304, No. 5.
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