Binding of Oligoguanylate to Scavenger Receptors Is Required for Oligonucleotides to Augment NK Cell Activity and Induce IFN

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Abstract
Specific palindromic sequences in synthetic oligonucleotides are required to induce IFN and augment IFN-meditated natural killer activity. To study the mechanism of IFN induction by oligonucleotides containing palindromic sequences, we investigated the possible target molecules of the oligonucleotides. Oligo-1, a 30mer single-stranded oligonuecleotide with oligoG sequences next to the active palindromic sequence (AACGTT), had more activity than oligonuecleotides with oligomer, oligoC, or oligoT sequences. The activity of oligo-1 was inhibited by a guanine homo-oligomer (G30), dextran sulfate, and polyvinyl sulfate. Oligo-1 bound to plastic-adherent mouse splenocytes, and the binding was inhibited by G30, dextran sulfate, and polyvinyl sulfate. Oligo-1bound to plastic-adherent mouse splenocytes, and the binding was inhibited by G30, dextran sulfate, and polyvinyl sulfate. Oligo-1 inhibited acetyl-LDL binding to the scavenger receptor on mouse splenocytes. These findings suggest that the binding of an extrapalindromic sequence to the scavenger receptor is required for the immunostimu-latory activity of oligo-1.

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