Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1989-3-28
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
142
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1755-66
pubmed:dateRevised
2011-11-17
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
pubmed:year
1989
pubmed:articleTitle
The role of ricin B chain in the intracellular trafficking of anti-CD5 immunotoxins.
pubmed:affiliation
Department of Therapeutic Radiology, University of Minnesota, Minneapolis 55455.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't