Mechanisms of DEAE-Dextran Enhancement of Polynucleotide Induction of Interferon 1

Discussion and Summary The present results demonstrate that, in the presence of an excess of DEAE-dx, In does not precipitate but it complexes with the polycation in a way which makes it resistant to pancreatic RNase. The formation of this type of complex may occur with other polycationic substances. Preliminary experiments show that high concentrations of neomycin produce a soluble complex, and poly-d-lysine at a change ratio of >30:1 also produces a soluble InCn-polycation (J. M. Rice, personal communication). It was also found that the induction of IF by the RNase-resistant complex was potentiated by the addition of DEAE-dx to the cell cultures. This indicates that protection of InCn against enzymatic degradation is not the sole mechanism by which IF production can be enhanced by DEAE-dx. It implies that DEAE-dx causes a large part of its enhancement by an effect on cells. Conceivably this could involve increased cellular uptake of the InCn as DEAE-dx does for other RNAs (5-7) but the need for such uptake has not been established. Additional evidence for a cell-mediated action of DEAE-dx comes from the previous observation that pretreatment of cells with DEAE-dx gave a maximal enhancing effect which could be abolished by brief contact of the treated cells with the polyanionic dextran sulfate (2). An RNase-resistant form of InCn may be useful in stimulating IF under conditions where RNase destruction of InCn is an important factor, such as in certain in vivo applications. This view is supported by the finding that sera from different species contain different amounts of depolymerizing enzymes and that some of them, including human serum, exert a substantial destructive effect on InCn (6).