A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin

Valeria V. Orlova, Eun Young Choi, Changping Xie, Emmanouil Chavakis, Angelika Bierhaus, Eveliina Ihanus, Christie M. Ballantyne, Carl G. Gahmberg, Marco E. Bianchi, Peter P. Nawroth, Triantafyllos Chavakis

Research output: Contribution to journalArticlepeer-review


High-mobility group box 1 (HMGB1) is released extracellularly upon cell necrosis acting as a mediator in tissue injury and inflammation. However, the molecular mechanisms for the proinflammatory effect of HMGB1 are poorly understood. Here, we define a novel function of HMGB1 in promoting Mac-1-dependent neutrophil recruitment. HMGB1 administration induced rapid neutrophil recruitment in vivo. HMGB1-mediated recruitment was prevented in mice deficient in the β2-integrin Mac-1 but not in those deficient in LFA-1. As observed by bone marrow chimera experiments, Mac-1-dependent neutrophil recruitment induced by HMGB1 required the presence of receptor for advanced glycation end products (RAGE) on neutrophils but not on endothelial cells. In vitro, HMGB1 enhanced the interaction between Mac-1 and RAGE. Consistently, HMGB1 activated Mac-1 as well as Mac-1-mediated adhesive and migratory functions of neutrophils in a RAGE-dependent manner. Moreover, HMGB1-induced activation of nuclear factor-κB in neutrophils required both Mac-1 and RAGE. Together, a novel HMGB1-dependent pathway for inflammatory cell recruitment and activation that requires the functional interplay between Mac-1 and RAGE is described here.

Original languageEnglish
Pages (from-to)1129-1139
Number of pages11
JournalEMBO Journal
Issue number4
Publication statusPublished - Feb 21 2007


  • Adhesion
  • Inflammation
  • Integrins
  • Neutrophils

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


Dive into the research topics of 'A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin'. Together they form a unique fingerprint.

Cite this