Combined treatment with Pseudomonas aeruginosa toxin and interferon on mouse and human cells

The combined biological effect of Pseudomonas toxin and beta-interferon on mammalian cells was studied on two cell lines. The first was a virus-producing clone derived from NIH/3T3 mouse fibroblasts transformed by Moloney murine sarcoma virus. The second was a clone derived from human amnion cells. The parameters examined were either retrovirus release from the mouse cells or the rate of protein synthesis in both cell lines. When applied together with Pseudomonas toxin, interferon inhibits virus release even at a Pseudomonas toxin concentration that by itself does not exhibit any biological effect on NIH/3T3 cells. This enhancement phenomenon is both Pseudomonas toxin and interferon dose-dependent. Likewise, the combined treatment of either mouse or human cells with Pseudomonas toxin and the appropriate species-specific interferon, inhibits protein synthesis to a much greater extent than either of these agents alone. The kinetics of the inhibition of virus release is different from that seen with protein synthesis indicating that the enhancement phenomenon observed on virus release is not a result of the inhibition of total cellular protein synthesis. Interferon potentiates the effect of Pseudomonas toxin in a species-specific manner, thus suggesting that this process does not occur at the level of cell receptors but is a consequence of a subsequent intracellular event. It is concluded that the enhancement phenomenon does not reflect a direct interaction between interferon and Pseudomonas toxin, since Pseudomonas incubated together with interferon retained its normal biological activity as indicated by the ability of the toxin molecule to transfer the adenine diphosphoribose (ADP-ribose) moiety of nicotinamide-adenine dinucleotide (NAD) onto elongation factor 2 (EF-2).