Journal article

HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4

  • Schiraldi, Milena Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Raucci, Angela Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy - HMGBiotech S.r.l., 20133 Milan, Italy
  • Martínez Muñoz, Laura Department of Immunology and Oncology, National Center for Biotechnology, Spanish National Research Council, 28049 Madrid, Spain
  • Livoti, Elsa Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Celona, Barbara HMGBiotech S.r.l., 20133 Milan, Italy
  • Venereau, Emilie Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy
  • Apuzzo, Tiziana Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • De Marchis, Francesco Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy
  • Pedotti, Mattia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Bachi, Angela Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy
  • Thelen, Marcus Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Varani, Luca Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Mellado, Mario Department of Immunology and Oncology, National Center for Biotechnology, Spanish National Research Council, 28049 Madrid, Spain
  • Proudfoot, Amanda Merck Serono S.A., 1202 Geneva, Switzerland
  • Bianchi, Marco Emilio Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy - Vita-Salute San Raffaele University, 20132 Milan, Italy
  • Uguccioni, Mariagrazia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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    27.02.2012
Published in:
  • The journal of experimental medicine. - 2012, vol. 209, no. 3, p. 551-563
English 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.
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  • English
Classification
Medicine
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https://susi.usi.ch/usi/documents/318882
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