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CUTTING EDGE |
*
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, CO 80262; and
Laboratory of Biomedical Science, North Shore University Hospital-New York University School of Medicine, Manhasset, NY 11030
Acute inflammatory lung injury is often a delayed complication
of critical illness and is associated with increased mortality. High
mobility group-1 (HMG-1) protein, in addition to its role as a
transcriptional regulatory factor, has recently been identified as a
late mediator of endotoxin lethality. In the present studies, HMG-1
given intratracheally produced acute inflammatory injury to the lungs,
with neutrophil accumulation, the development of lung edema, and
increased pulmonary production of IL-1ß, TNF-
, and
macrophage-inflammatory protein-2. In endotoxin-induced acute lung
inflammation, administration of anti-HMG-1 Abs either before or
after endotoxin exposure decreased the migration of neutrophils to the
lungs as well as lung edema. These protective effects of anti-HMG-1
were specific, because pulmonary levels of IL-1ß, TNF-, or
macrophage-inflammatory protein-2 were not decreased after therapy with
anti-HMG-1. Together, these findings indicate that HMG-1 is a
distal mediator of acute inflammatory lung
injury.
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L. Ulloa, M. Ochani, H. Yang, M. Tanovic, D. Halperin, R. Yang, C. J. Czura, M. P. Fink, and K. J. Tracey Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation PNAS, September 17, 2002; 99(19): 12351 - 12356. [Abstract] [Full Text] [PDF]
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H. WANG, H. YANG, C. J. CZURA, A. E. SAMA, and K. J. TRACEY HMGB1 as a Late Mediator of Lethal Systemic Inflammation Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1768 - 1773. [Full Text] [PDF]
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J. Fan, R. D. Ye, and A. B. Malik Transcriptional mechanisms of acute lung injury Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1037 - L1050. [Abstract] [Full Text] [PDF]
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C. J. Czura, Haichao Wang, and K. J. Tracey Dual roles for HMGB1: DNA binding and cytokine Innate Immunity, August 1, 2001; 7(4): 315 - 321. [Abstract] [PDF]
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B. Degryse, T. Bonaldi, P. Scaffidi, S. Muller, M. Resnati, F. Sanvito, G. Arrigoni, and M. E. Bianchi The High Mobility Group (HMG) Boxes of the Nuclear Protein HMG1 Induce Chemotaxis and Cytoskeleton Reorganization in Rat Smooth Muscle Cells J. Cell Biol., March 19, 2001; 152(6): 1197 - 1206. [Abstract] [Full Text] [PDF]
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