title: A low level of TNF-alpha mediates hemorrhage-induced acute lung injury via p55 TNF receptor.
abstract: Acute lung injury after hemorrhagic shock (HS) is associated with the expression of tumor necrosis factor (TNF)-alpha in the lung. However, the role of TNF-alpha and its receptors in this pulmonary disorder remains obscure. This study examined the temporal relationship of pulmonary TNF-alpha production to neutrophil accumulation during HS and determined the role of TNF-alpha in neutrophil accumulation and lung leak. HS was induced in mice by removal of 30% of total blood volume. Lung TNF-alpha was measured by ELISA. Neutrophil accumulation was detected by immunofluorescent staining, and microvascular permeability was assessed using Evans blue dye. Although HS induced a slight and transient increase in lung TNF-alpha, neutrophil accumulation preceded the increase in TNF-alpha. However, lung neutrophil accumulation and lung leak were abrogated in TNF-alpha knockout mice, and both were restored by administration of recombinant TNF-alpha to TNF-alpha knockout mice before HS. Neutrophil accumulation and lung leak were abrogated in mice lacking the p55 TNF-alpha receptor, but neither was influenced by p75 TNF-alpha receptor knockout. This study demonstrates that a low level of pulmonary TNF-alpha is sufficient to mediate HS-induced acute lung injury during HS and that the p55 TNF-alpha receptor plays a dominant role in regulating the pulmonary inflammatory response to HS.
authors.affiliation: Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: L
authors.initials: L
authors.lastname: Ao
authors.forename: C D
authors.initials: CD
authors.lastname: Raeburn
authors.forename: C M
authors.initials: CM
authors.lastname: Calkins
authors.forename: E
authors.initials: E
authors.lastname: Abraham
authors.forename: A H
authors.initials: AH
authors.lastname: Harken
authors.forename: X
authors.initials: X
authors.lastname: Meng
mesh_terms: D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D006470:Hemorrhage / Q000150:complications*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009504:Neutrophils / Q000502:physiology; D010539:Permeability; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012771:Shock, Hemorrhagic / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha