title: Interacting neuroendocrine and innate and acquired immune pathways regulate neutrophil mobilization from bone marrow following hemorrhagic shock.
abstract: Polymorphonuclear neutrophils (PMN) are critical innate immune effector cells that either protect the host or exacerbate organ dysfunction by migrating to injured or inflamed tissues. Resuscitated hemorrhagic shock following major trauma promotes the development of organ inflammation by priming PMN migration and activation in response to a second, often trivial, stimulus (a so-called "two hit" phenomenon). PMN mobilization from bone marrow supports a sustained, hemorrhagic shock/resuscitation (HS/R)-primed migration of PMN. We addressed the role and mechanism of HS/R in regulating PMN egress from bone marrow. We demonstrate that HS/R through the alarmin HMGB1 induces IL-23 secretion from macrophages in an autocrine and TLR4 signaling-dependent manner. In turn IL-23, through an IL-17 G-CSF-mediated mechanism, induces PMN egress from bone marrow. We also show that beta-adrenergic receptor activation by catecholamine of macrophages mediates the HS/R-induced release of HMGB1. These data indicate that HS/R, a global ischemia/reperfusion stimulus, regulates PMN mobilization through a series of interacting pathways that include neuroendocrine and innate and acquired immune systems. Blocking this novel signaling axis may present a novel therapeutic target for posttrauma inflammation.
authors.affiliation: Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Yujian
authors.initials: Y
authors.lastname: Liu
authors.forename: Youzhong
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Guozhi
authors.initials: G
authors.lastname: Xiao
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wilson
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D004837:Epinephrine / Q000502:physiology; D024243:HMGB1 Protein / Q000378:metabolism / Q000502:physiology; D007113:Immunity, Innate; D053759:Interleukin-23 / Q000378:metabolism / Q000502:physiology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009490:Neurosecretory Systems / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000276:immunology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D024243:HMGB1 Protein; D053759:Interleukin-23; D011943:Receptors, Adrenergic, beta; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D004837:Epinephrine