Endotoxin stimulates expression of the murine urokinase receptor gene in vivo.
The regulation of urokinase receptor (u-PAR) gene expression during endotoxemia was studied in vivo with a murine model system. Northern blot analysis demonstrated relatively high levels of u-PAR mRNA in mouse placenta, with intermediate levels in lung and spleen and very low levels in heart and kidney. No u-PAR mRNA could be detected in liver, gut, thymus, brain, or skeletal muscle. Intraperitoneal injection of endotoxin (lipopolysaccharide) increased the steady-state levels of u-PAR mRNA in most tissues examined. The greatest induction (sevenfold) was observed in the lung at 1 hour after injection. The cellular localization of u-PAR mRNA was assessed by in situ hybridization. In control mice, u-PAR mRNA was detected primarily in alveolar macrophages of the lung and lymphocytes of the spleen and thymus, although a specific signal was also present in other cell types. In general, endothelial cells lacked detectable u-PAR mRNA. The induction of u-PAR mRNA by lipopolysaccharide was apparent within 30 minutes and was localized to tissue macrophages, lymphocytes, and endothelial cells lining arteries and veins. At later times (1 to 3 hours), specialized epithelial cells present in gastrointestinal tract, bile ducts, and uterus were also positive for u-PAR mRNA. Induction of u-PAR in vivo by lipopolysaccharide may facilitate the extravasation and migration of leukocytes during inflammation.
Almus-Jacobs
F
F
Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Varki
N
N
Sawdey
M S
MS
Loskutoff
D J
DJ
D000818:Animals; D001483:Base Sequence; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D014018:Tissue Distribution; D014158:Transcription, Genetic
D004731:Endotoxins; D008070:Lipopolysaccharides; D015335:Molecular Probes; C524899:Plaur protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator