Increases in lung tissue expression of intercellular adhesion molecule-1 are associated with hyperoxic lung injury and inflammation in mice.
Lung injury caused by breathing enriched oxygen continues to be a major problem in clinical medicine. Experimentally, hyperoxic lung injury is characterized by pulmonary edema and associated neutrophil accumulation. Although extensively investigated, the mechanisms for neutrophil accumulation and the role of this accumulation in hyperoxic lung injury remain controversial. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that when increased on endothelium by inflammatory cytokines leads to increased adhesion of neutrophils to the inflamed endothelium and transendothelial migration. The purpose of this study was to examine the role of inflammation in hyperoxia-induced lung injury by investigating ICAM-1 expression in the lungs of mice exposed to > 95% oxygen continuously. Lung tissue from mice exposed to > 95% oxygen was analyzed for ICAM-1 mRNA by slot blot analysis and for ICAM-1 protein expression. We also examined lungs from mice exposed to hyperoxia for up to 96 h by light microscopy to correlate pulmonary inflammation with ICAM-1 expression. We found that mRNA for ICAM-1 increased 56% over baseline after 48 h of exposure to hyperoxia, that ICAM-1 protein increased by more than 5-fold over baseline after 96 h of exposure to hyperoxia, and that lung inflammation and injury were not evident until 96 h of exposure. Our data demonstrate that exposure to hyperoxia causes an increase in ICAM-1 gene transcription and/or mRNA stability in mouse lungs, and that this increase is followed by an increase in ICAM-1 protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Welty
S E
SE
Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Rivera
J L
JL
Elliston
J F
JF
Smith
C V
CV
Zeb
T
T
Ballantyne
C M
CM
Montgomery
C A
CA
Hansen
T N
TN
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D018799:Intercellular Adhesion Molecule-1; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D010100:Oxygen / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; D010100:Oxygen