title: Platelet-derived high-mobility group box 1 promotes recruitment and suppresses apoptosis of monocytes.
abstract: Platelets are circulating cellular sensors that express and release the damage-associated molecular pattern molecule (DAMP) high-mobility group box 1 (HMGB1) at sites of disrupted vascular and tissue integrity. We have recently identified platelet-derived HMGB1 as a critical mediator of thrombosis. The role of platelet-derived HMGB1 in mediating interactions with monocytes remains unknown. In transgenic mice with platelet-specific ablation of HMGB1 and neutralization studies, we show that HMGB1 derived from platelets promotes recruitment of monocytes and prevents monocytes from undergoing apoptosis. During experimental trauma and hemorrhagic shock, infiltrated monocytes in the lung and liver were significantly attenuated in mice lacking HMGB1 in platelets. Platelet-derived HMGB1 mediated monocyte migration via the receptor for advanced glycation end products (RAGE) and suppressed apoptosis via toll-like receptor 4 (TLR4)-dependent activation of MAPK/ERK (extracellular signal-regulated kinase) in monocytes. In conclusion, we identify platelet-derived HMGB1 as a critical regulator of monocyte recruitment and apoptosis, with potential implications in disease states associated with thrombosis and inflammation.
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany. Electronic address: sebastian.vogel@med.uni-tuebingen.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rath
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
authors.affiliation: Institute of Anatomy, Eberhard Karls University Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mack
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Loughran
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Neal
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.affiliation: Department of Cardiology and Cardiovascular Diseases, Eberhard Karls University Tübingen, Germany.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D024243:HMGB1 Protein / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: C000593873:Ager protein, mouse; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D000067759:Receptor for Advanced Glycation End Products; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: Apoptosis; High-mobility group box 1; Migration; Monocytes; Platelets