Localization of 2',5'-oligoadenylate synthetase and the enhancement of its activity with recombinant interferon-alpha A/D in the mouse brain

Abstract

Although the expression of 2',5'-oligoadenylate synthetase (2-5AS) is induced by interferon (IFN), low constitutive levels can be detected in animals that have not been treated with IFN. In order to clarify which cells express 2-5AS in the mouse brain, the distribution of this enzyme in the brains of both normal healthy mice and mice treated with recombinant human IFN-alpha A/D was studied by Western blotting and immunohistochemistry, using a specific monoclonal antibody. On the Western blots, the antibody to 42-kD 2-5AS reacted slightly with extracts from the telencephalon, cerebellum, diencephalon, and medulla oblongata of normal mouse brain. 42-kD 2-5AS was predominantly found in the ependymal cells and epithelium of the choroid plexus, and to a lesser degree in neurons and glial cells. Injection of recombinant human IFN-alpha A/D into the left lateral ventricle enhanced the activity of the enzyme in the telencephalon, cerebellum, diencephalon, and medulla oblongata, but did not change the immunohistochemical localization of the enzyme. Direct injection of the IFN into the cortex of the telencephalon enhanced the activity of 2-5AS in all parts of the brain and immunoreactivity was observed in the neurons and glial cells surrounding the injection site. These data indicate that 42-kD 2-5AS activity in the mouse brain is enhanced by the injection of recombinant human IFN-alpha A/D either into the left lateral ventricle or cortex of the telencephalon. Expression of 42-kD 2-5AS in ependymal cells and epithelium of the choroid plexus may prevent viral infections in the brain.