Increased endothelial cell expression of platelet-endothelial cell adhesion molecule-1 during hyperoxic lung injury.
Lung injury is a frequent consequence of oxygen (O2) therapy administered to newborns and adults with respiratory distress. Acute exposure to hyperoxia results in a well-described pathophysiologic response in the lungs. Because inflammation is an important component of pulmonary O2 toxicity, we have an interest in identifying the inflammatory mediators that increase during hyperoxia. Platelet-endothelial cell adhesion molecule-1 (PECAM-1), a member of the immunoglobulin superfamily that is expressed at the junctions between endothelial cells, is essential to the transendothelial migration of leukocytes. We hypothesized that increased expression of PECAM-1 occurs in pulmonary endothelial cells during hyperoxic lung injury. Adult mice were exposed to 100% O2 for up to 96 h. We analyzed PECAM-1 expression by RNA blot hybridization, in situ hybridization, and immunohistochemistry. A increase in PECAM-1 mRNA was seen as soon as 2 d of hyperoxia relative to unexposed control mice. PECAM-1 mRNA and protein were found in endothelial cells of both large and small arteries. The expression of PECAM-1 in capillary vessels was further confirmed using in situ hybridization at the electron microscope level. This increase in PECAM-1 expression coincided with the appearance of leukocytes in lung tissue. These observations suggest that PECAM-1 expression is a relatively early step in the inflammation cascade, and intervention at this phase may be critical to the prevention of further damage.
Piedboeuf
B
B
Department of Pediatrics, Centre de Recherche du CHUL, Centre Hospitalier Universitaire de Québec, Sainte Foy, Québec, Canada. Bruno.Piedboeuf@crchul.ulaval.ca
Gamache
M
M
Frenette
J
J
Horowitz
S
S
Baldwin
H S
HS
Petrov
P
P
D017398:Alternative Splicing / Q000276:immunology; D000818:Animals; D015153:Blotting, Western; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D018496:Hyperoxia / Q000276:immunology / Q000503:physiopathology; D017403:In Situ Hybridization; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016253:Microscopy, Immunoelectron; D010100:Oxygen / Q000633:toxicity*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D010100:Oxygen