Effect of an anti-murine transferrin receptor-ricin A conjugate on bone marrow stem and progenitor cells treated in vitro.
A monoclonal antibody with specificity for murine transferrin receptor was conjugated with the toxic A subunit of ricin. The dose range, specificity, and kinetics of inhibition of protein synthesis of the conjugate were determined on the murine T-lymphoma cell line, BW5147. When toxin was present throughout the period of culture, in vitro myeloid (CFUc) and erythroid (CFUe and BFUe) bone marrow colonies were inhibited by doses of conjugate comparable to those that inhibit protein synthesis in murine cell lines (IC50 of 5 X 10(-11)M). Bone marrow exposed briefly (30 min to 6 h) to anti-transferrin receptor antibody-ricin A conjugate was assayed for myeloid (CFUc) and erythroid (CFUe and BFUe) progenitors in vitro and for in vivo spleen colony formation (CFUs). Only CFUe were depleted by this pulse exposure, consistent with the higher frequency of proliferating cells and transferrin receptor expression in the CFUe population relative to other progenitors.
D000818:Animals; D000911:Antibodies, Monoclonal; D002455:Cell Division; D002460:Cell Line; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007938:Leukemia; D008223:Lymphoma; D051379:Mice; D011956:Receptors, Cell Surface / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D011990:Receptors, Transferrin; D012276:Ricin; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes
D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D012276:Ricin