HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4
Open Access
- 27 February 2012
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 209 (3), 551-563
- https://doi.org/10.1084/jem.20111739
Abstract
After tissue damage, inflammatory cells infiltrate the tissue and release proinflammatory cytokines. HMGB1 (high mobility group box 1), a nuclear protein released by necrotic and severely stressed cells, promotes cytokine release via its interaction with the TLR4 (Toll-like receptor 4) receptor and cell migration via an unknown mechanism. We show that HMGB1-induced recruitment of inflammatory cells depends on CXCL12. HMGB1 and CXCL12 form a heterocomplex, which we characterized by nuclear magnetic resonance and surface plasmon resonance, that acts exclusively through CXCR4 and not through other HMGB1 receptors. Fluorescence resonance energy transfer data show that the HMGB1–CXCL12 heterocomplex promotes different conformational rearrangements of CXCR4 from that of CXCL12 alone. Mononuclear cell recruitment in vivo into air pouches and injured muscles depends on the heterocomplex and is inhibited by AMD3100 and glycyrrhizin. Thus, inflammatory cell recruitment and activation both depend on HMGB1 via different mechanisms.This publication has 51 references indexed in Scilit:
- Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide AntagonistsScience, 2010
- Endogenous HMGB1 regulates autophagyThe Journal of cell biology, 2010
- CXCR4 blockade augments bone marrow progenitor cell recruitment to the neovasculature and reduces mortality after myocardial infarctionProceedings of the National Academy of Sciences of the United States of America, 2010
- A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine releaseProceedings of the National Academy of Sciences of the United States of America, 2010
- HMGB1 release induced by liver ischemia involves Toll-like receptor 4–dependent reactive oxygen species production and calcium-mediated signalingThe Journal of Experimental Medicine, 2007
- Toll-like receptor 4–dependent contribution of the immune system to anticancer chemotherapy and radiotherapyNature Medicine, 2007
- Solution mapping of T cell receptor docking footprints on peptide-MHCProceedings of the National Academy of Sciences of the United States of America, 2007
- Activation of Poly(ADP)-ribose Polymerase (PARP-1) Induces Release of the Pro-inflammatory Mediator HMGB1 from the NucleusOnline Journal of Public Health Informatics, 2007
- A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrinThe EMBO Journal, 2007
- Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar developmentNature, 1998