Faculty Collaboration Database

A low level of TNF-alpha mediates hemorrhage-induced acute lung injury via p55 TNF receptor. Am J Physiol Lung Cell Mol Physiol 2001 Sep;281(3):L677-84

Date

08/16/2001

Pubmed ID

11504696

DOI

10.1152/ajplung.2001.281.3.L677

Scopus ID

2-s2.0-0034829202 (requires institutional sign-in at Scopus site)   61 Citations

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.

Author List

Song Y, Ao L, Raeburn CD, Calkins CM, Abraham E, Harken AH, Meng X

Author

Casey Matthew Calkins MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Animals
Antigens, CD
Cell Movement
Hemorrhage
Lung
Lung Diseases
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils
Permeability
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Shock, Hemorrhagic
Time Factors
Tumor Necrosis Factor-alpha