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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1989-3-28
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pubmed:abstractText |
The mAb anti-CD5 was linked to purified ricin A chain (RTA) or intact ricin (Rc) containing B chain to determine the role of ricin B chain in the intracellular trafficking of anti-CD5 immunotoxins (IT). IT were radiolabeled with iodine-125 and then studied for their subcellular compartmentalization in an acute lymphoblastic leukemia T cell line, CEM. Ricin A chain IT was not as toxic to CEM cells as Rc-IT in protein synthesis inhibition assays. This difference was not attributed to differential binding or modulation of the CD5 determinant from the cell surface as measured by FACS analysis. However, we found a relationship between the toxicity of anti-CD5-Rc and anti-CD5-RTA and their ability to traffic to CEM lysosomes. Kinetic analysis of the transfer of radioimmunotoxin to the lysosomes showed that anti-CD5-Rc was trafficked significantly more slowly than anti-CD5-RTA, perhaps due to an extended period of time in the Golgi compartment. The possibility of a Golgi interaction was tested by adding monensin, a carboxylic ionophore that interrupts trafficking through the Golgi, to cells treated with anti-CD5-RTA. The addition of monensin caused anti-CD5-RTA to traffic in a manner identical to anti-CD5-Rc. We conclude that 1) B chain slows trafficking of anti-CD5-Rc to the lysosomes; 2) the rate-limiting step in the toxicity difference between anti-CD5-Rc and anti-CD5-RTA is the rate of transfer to the lysosomes; and 3) trafficking through the Golgi may be important for anti-CD5-IT toxicity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD5,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Immunotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Ricin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
142
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1755-66
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:2465347-Animals,
pubmed-meshheading:2465347-Antibodies, Monoclonal,
pubmed-meshheading:2465347-Antigens, CD5,
pubmed-meshheading:2465347-Antigens, Differentiation,
pubmed-meshheading:2465347-Binding, Competitive,
pubmed-meshheading:2465347-Binding Sites, Antibody,
pubmed-meshheading:2465347-Cell Line,
pubmed-meshheading:2465347-Cell-Free System,
pubmed-meshheading:2465347-Centrifugation, Density Gradient,
pubmed-meshheading:2465347-Endocytosis,
pubmed-meshheading:2465347-Fluorescent Antibody Technique,
pubmed-meshheading:2465347-Humans,
pubmed-meshheading:2465347-Immunotoxins,
pubmed-meshheading:2465347-Kinetics,
pubmed-meshheading:2465347-Lysosomes,
pubmed-meshheading:2465347-Mice,
pubmed-meshheading:2465347-Protein Synthesis Inhibitors,
pubmed-meshheading:2465347-Receptors, Antigen, T-Cell,
pubmed-meshheading:2465347-Ricin
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pubmed:year |
1989
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pubmed:articleTitle |
The role of ricin B chain in the intracellular trafficking of anti-CD5 immunotoxins.
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pubmed:affiliation |
Department of Therapeutic Radiology, University of Minnesota, Minneapolis 55455.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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