Nuclear HMGB1 promotes the phagocytic ability of macrophages

Exp Cell Res. 2020 Aug 1;393(1):112037. doi: 10.1016/j.yexcr.2020.112037. Epub 2020 Apr 28.

Abstract

Phagocytosis is a basic immune response to the invasion of pathogens. High mobility group protein B1 (HMGB1) is a DNA chaperone that is associated with phagocytosis. However, its influence on phagocytosis is debated. In the present study, HMGB1-mutant, HMGB1-overexpressing and HMGB1-silenced RAW264.7 cells were constructed. In addition, HMGB1 conditional knockout mice were constructed to determine the influence of HMGB1 on phagocytosis. Lipopolysaccharide (LPS) was used to stimulate the translocation of HMGB1 from the nucleus to the cytoplasm. Zymosan particles were used to test the phagocytic function of the macrophages. Our results showed that the accumulation of HMGB1 in the nucleus enhances the phagocytic function of the macrophages. By interacting with P53, nuclear HMGB1 may remain in the nucleus and decrease the negative influence of P53 on the phosphorylation of focal adhesion kinase (FAK). The increase in phosphorylated FAK promotes the formation of pseudopods and enhances the phagocytic ability of macrophages.

Keywords: FAK; HMGB1; Macrophage; P53; Phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • HMGB1 Protein / metabolism*
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Phagocytosis / drug effects
  • Phagocytosis / physiology*
  • Protein Transport / drug effects
  • Protein Transport / physiology*

Substances

  • HMGB1 Protein
  • HMGB1 protein, mouse
  • Lipopolysaccharides
  • NF-kappa B