HMG-1 as a mediator of acute lung inflammation.
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-1beta, TNF-alpha, 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-1beta, TNF-alpha, 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.
Abraham
E
E
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. edward.abraham@uchsc.edu
Arcaroli
J
J
Carmody
A
A
Wang
H
H
Tracey
K J
KJ
D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004731:Endotoxins / Q000633:toxicity; D006609:High Mobility Group Proteins / Q000276:immunology / Q000633:toxicity*; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D007442:Intubation, Intratracheal; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009928:Organ Specificity / Q000276:immunology; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D004731:Endotoxins; D006609:High Mobility Group Proteins; D007106:Immune Sera; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha