HMG-1 as a Late Mediator of Endotoxin Lethality in Mice

DOI Web Site 被引用文献240件
  • Haichao Wang
    Department of Emergency Medicine and
  • Ona Bloom
    The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
  • Minghuang Zhang
    The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
  • Jaideep M. Vishnubhakat
    The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
  • Michael Ombrellino
    Department of Surgery, North Shore University Hospital–New York University School of Medicine, Manhasset, NY 11030, USA.
  • Jiantu Che
    The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
  • Asia Frazier
    Department of Surgery, North Shore University Hospital–New York University School of Medicine, Manhasset, NY 11030, USA.
  • Huan Yang
    The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
  • Svetlana Ivanova
    The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
  • Lyudmila Borovikova
    The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
  • Kirk R. Manogue
    The Picower Institute for Medical Research, Manhasset, NY 11030, USA.
  • Eugen Faist
    Department of Surgery, Klinicum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
  • Edward Abraham
    Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
  • Jan Andersson
    Department of Infectious Disease, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
  • Ulf Andersson
    Department of Rheumatology, Astrid Lindgren's Children's Hospital, Karolinska Institute, Stockholm, Sweden.
  • Patricia E. Molina
    Department of Surgery, North Shore University Hospital–New York University School of Medicine, Manhasset, NY 11030, USA.
  • Naji N. Abumrad
    Department of Surgery, North Shore University Hospital–New York University School of Medicine, Manhasset, NY 11030, USA.
  • Andrew Sama
    Department of Emergency Medicine and
  • Kevin J. Tracey
    Department of Surgery, North Shore University Hospital–New York University School of Medicine, Manhasset, NY 11030, USA.

抄録

<jats:p>Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group–1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.</jats:p>

収録刊行物

  • Science

    Science 285 (5425), 248-251, 1999-07-09

    American Association for the Advancement of Science (AAAS)

被引用文献 (240)*注記

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