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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
34
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pubmed:dateCreated |
1989-1-3
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pubmed:abstractText |
The interaction in vivo of 125I-labeled tissue-type plasminogen activator (t-PA) with the rat liver and the various liver cell types was characterized. Intravenously injected 125I-t-PA was rapidly cleared from the plasma (t1/2 = 1 min), and 80% of the injected dose associated with the liver. After uptake, t-PA was rapidly degraded in the lysosomes. The interaction of 125I-t-PA with the liver could be inhibited by preinjection of the rats with ovalbumin or unlabeled t-PA. The intrahepatic recognition site(s) for t-PA were determined by subfractionation of the liver in parenchymal, endothelial, and Kupffer cells. It can be calculated that parenchymal cells are responsible for 54.5% of the interaction of t-PA with the liver, endothelial cells for 39.5%, and Kupffer cells for only 6%. The association of t-PA with parenchymal cells was not mediated by a carbohydrate-specific receptor and could only be inhibited by an excess of unlabeled t-PA, indicating involvement of a specific t-PA recognition site. The association of t-PA with endothelial cells could be inhibited 80% by the mannose-terminated glycoprotein ovalbumin, suggesting that the mannose receptor plays a major role in the recognition of t-PA by endothelial liver cells. An excess of unlabeled t-PA inhibited the association of 125I-t-PA to endothelial liver cells 95%, indicating that an additional specific t-PA recognition site may be responsible for 15% of the high affinity interaction of t-PA with this liver cell type. It is concluded that the uptake of t-PA by the liver is mainly mediated by two recognition systems: a specific t-PA site on parenchymal cells and the mannose receptor on endothelial liver cells. It is suggested that for the development of strategies to prolong the half-life of t-PA in the blood, the presence of both types of recognition systems has to be taken into account.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
263
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18220-4
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:3142872-Animals,
pubmed-meshheading:3142872-Biological Transport,
pubmed-meshheading:3142872-Cell Membrane,
pubmed-meshheading:3142872-Iodine Radioisotopes,
pubmed-meshheading:3142872-Kinetics,
pubmed-meshheading:3142872-Liver,
pubmed-meshheading:3142872-Male,
pubmed-meshheading:3142872-Metabolic Clearance Rate,
pubmed-meshheading:3142872-Ovalbumin,
pubmed-meshheading:3142872-Rats,
pubmed-meshheading:3142872-Rats, Inbred Strains,
pubmed-meshheading:3142872-Tissue Plasminogen Activator
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pubmed:year |
1988
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pubmed:articleTitle |
Characterization of the interaction in vivo of tissue-type plasminogen activator with liver cells.
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pubmed:affiliation |
Division of Biopharmaceutic, Sylvius Laboratories, University of Leiden, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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