Analysis of Ia induction on Lewis rat astrocytes in vitro by virus particles and bacterial adjuvants

Viral particles of a neurotropic murine hepatitis virus (JHM) and various substances known to have immunoregulatory effects, including bacterial lipopolysaccharide (LPS) and synthetic adjuvant peptide (muramyl dipeptide) (AP), were tested for their ability to induce Ia antigen expression on Lewis rat astrocytes in vitro. JHM virus, LPS and AP are all capable of inducing Ia molecules on astrocytes, however, in a pattern and kinetics distinct from recombinant rat gamma interferon (γ-IFN). Whereas γ-IFN induced Ia expression on astrocytes and all macrophages after 48 h treatment, JHM virus, LPS and AP required 4–7 days for maximal induction of Ia on astrocytes, but had little to no effect on the macrophage population. This indicates that astrocytes are uniquely reactive to components derived from infectious agents and that these components are immunoregulatory with respect to Ia expression on astrocytes. We have also attempted to determine possible mechanisms by which these agents induce astrocyte Ia and show that phorbol myristate acetate and Ca(2+) ionophore A23187 have similar effects. These findings suggest that infectious agents may directly stimulate antigen presenting functions of astrocytes in the brain through γ-IFN-independent mechanisms.