Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo.
The tissue-specific distribution of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) and their inhibitor type 1 (PAI-1) was analyzed at mRNA level in five major rat organ tissues. t-PA mRNA was detected in lung, kidney, heart, and liver. u-PA mRNA was detected in kidney and lung. Presence of PA mRNA correlated with the detection of PA activity in extracts of these tissues. PAI-1 mRNA was detected predominantly in heart and lung. Although PAI activity could not be measured directly in tissue extracts, the presence of PAI-1 mRNA correlated with the occurrence of PA.PAI complex in fibrin autography of tissue extracts. Endotoxin injection caused a very large increase in plasma PAI activity. This increase correlated with a marked increase in PAI-1 mRNA in nearly all tissues studied. The increase in PAI-1 mRNA is most pronounced in lung and liver. Endotoxin injection also caused an increased level of t-PA mRNA in heart and kidney, and an increased u-PA mRNA level in kidney. mRNA analysis of freshly isolated and separated subfractionated liver cells showed that the marked increase in PAI-1 mRNA in the liver after endotoxin injection may be due mainly to a strong increase of PAI-1 mRNA in the liver endothelial cells.
Quax
P H
PH
Gaubius Institute TNO, Leiden, The Netherlands.
van den Hoogen
C M
CM
Verheijen
J H
JH
Padro
T
T
Zeheb
R
R
Gelehrter
T D
TD
van Berkel
T J
TJ
Kuiper
J
J
Emeis
J J
JJ
D000818:Animals; D015152:Blotting, Northern; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D010960:Plasminogen Activators / Q000235:genetics*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D004731:Endotoxins; D015849:Plasminogen Inactivators; D011498:Protein Precursors; D012333:RNA, Messenger; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator