The response of cultured mammalian cells to diphtheria toxin. II. The resistant cell: enhancement of toxin action by poly-L-ornithine.

We have investigated the response of the resistant mouse L cell to diphtheria toxin. Intact cells and cell-free systems were studied. It was determined that the cell-free system is as sensitive to toxin as those from sensitive reticulocyte, HeLa, and KB cells previously studied. Poly-L-ornithine, reported to stimulate macromolecular uptake, enhanced toxin activity under conditions which also stimulated acid phosphatase activity. Resistance, in the L cell, appears to be linked to the cell membrane and the process of macromolecular uptake, and not to any intrinsic property of either the polyribosomes or associated protein synthesizing factors. Because of the unique way in which diphtheria toxin inhibits protein synthesis, the ability of poly-L-ornthine to enhance this action provides convincing evidence that poly-L-ornithine stimulates a true absorption of macromolecules and not just increased surface adsorption.