INTERFERON-GAMMA UP-REGULATES ALPHA(2) MACROGLOBULIN EXPRESSION IN HUMAN ASTROCYTOMA-CELLS

An established human astrocytoma cell line (T67) was shown to constitu tively produce the proteinase inhibitor cr,macroglobulin (alpha(2)M). Interferon gamma (IFN gamma), a potent immunoregulatory lymphokine, wa s able to increase the synthesis of alpha(2)M by these cells, as measu red by ELISA on cell supernatants. The alpha(2)M induction was also ob served in other human glioma cell lines (T70 and ADF) and in human fet al astrocyte cultures following IFN gamma treatment. In T67 cells this effect was dose-dependent and the maximum (2.7-fold increase) was obt ained with 2000 U/ml of IFN gamma. A corresponding enhanced alpha(2)M mRNA accumulation was demonstrated by PCR and Northern blot techniques . Our results suggest an important role of alpha(2)M during inflammato ry and immune processes in the CNS. An increased release of alpha(2)M following IFN gamma stimulation may allow the removal of the bulk of p roteases released at the site of inflammation, strengthening at the sa me time the antigen presentation processes.