| Internalization and intracellular fate of anti-CD5 monoclonal antibody and anti-CD5 ricin A-chain immunotoxin in human leukemic T cells. | |
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MedLine Citation:
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PMID: 1372189 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have investigated the entry and subsequent intracellular fate of T101 monoclonal antibody (MoAb) and T101-ricin A-chain (RTA) immunotoxin (IT) directed against the CD5 antigen (Ag) expressed on human leukemic CEM cells. We provide direct evidence for the internalization of T101 MoAb and the corresponding IT. Both the MoAb and IT were internalized at a relatively low rate. This slow internalization process could be related to the partial recycling of the MoAb/Ag or IT/Ag complexes. Analysis of the internalized molecules showed that their molecular weight was only partially altered after internalization and that no free A-chain could be found inside the cells, indicating that lysosomal degradation and cleavage of disulfide-linked conjugates is a quantitatively minor phenomenon compared with the localization of internalized anti-CD5 ITs in an endosomo-Golgi compartment, followed by their recycling to the cell surface. We believe that this is the major factor explaining the low efficacy of anti-CD5 IT when assayed in the absence of potentiating substances. Finally, we showed that the presence of ammonium chloride and monensin, which both dramatically enhance the kinetics of IT activity, did not affect the rate of internalization or the intracellular localization of the conjugate, suggesting that these activators could act at the postendocytotic level on a limited number of IT molecules. |
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Authors:
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S Ravel; M Colombatti; P Casellas |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Blood Volume: 79 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 1992 Mar |
Date Detail:
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Created Date: 1992-04-17 Completed Date: 1992-04-17 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1511-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Immunology, Sanofi Recherche, Montpellier, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Ammonium Chloride
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pharmacology Animals Antibodies, Monoclonal* Antigens, CD / immunology* Antigens, CD5 Golgi Apparatus / metabolism Humans Immunotoxins / metabolism* Leukemia / metabolism* Lysosomes / metabolism Mice Monensin / pharmacology Ricin / metabolism* T-Lymphocytes / metabolism*, ultrastructure |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antigens, CD; 0/Antigens, CD5; 0/Immunotoxins; 12125-02-9/Ammonium Chloride; 17090-79-8/Monensin; 9009-86-3/Ricin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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