CHARACTERIZATION OF A SAPORIN MITOTOXIN SPECIFICALLY CYTOTOXIC TO CELLS BEARING THE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR

When granulocyte-macrophage colony-stimulating factor (GM-CSF) is chem ically conjugated to the ribosome-inactivating protein saporin, the re sulting protein conjugate is highly toxic for cells expressing the GM- CSF receptor. Structural and Western blot analyses of the purified con jugate establish that it contains equimolar amounts of the starting ma terials and is free of any contamination by the non-conjugated compone nts. The resulting bifunctional reagent is specifically cytotoxic to c ells expressing the GM-CSF receptor, but is ineffective to cells that do not express the receptor. The cytotoxic activity is inhibited in a dose-dependent manner by GM-CSF, but not by any one of five other pept ide growth factors. This is the first report of a mitotoxin for cells that express the GM-CSF receptor and which promises to be a valuable t ool to study the expression of the GM-CSF receptor in normal and patho logical states.