HEPARIN INHIBITS THE ANTIPARASITIC AND IMMUNE MODULATORY EFFECTS OF HUMAN RECOMBINANT INTERFERON-GAMMA

Interferon-gamma (IFN-gamma) is a potent immune regulatory cytokine an d is, in addition, involved in the induction of antiparasitic effector mechanisms in different cell types. The first step of IFN-gamma actio n is its binding to a specific receptor. Furthermore, it has been show n that IFN-gamma binds with a great affinity to the heparin-like struc ture of heparan sulfate, which is localized in basement membranes and on cell surfaces. In this study, we analyze the effect of heparin and heparan sulfate on three different IFN-gamma-mediated activities induc ible in human glioblastoma cells (87HG31 and 86HG39). We find firstly that heparin is able to inhibit IFN-gamma-mediated induction of major histocompatibility complex (MHC) class II antigen expression on 87HG31 cells, an effect which can be abrogated by protamine. Secondly, we sh ow that heparin inhibits the IFN-gamma-induced toxoplasmostasis within 86HG39 cells in a dose-dependent fashion, and thirdly that heparin in hibits the IFN-gamma-mediated induction of the tryptophan-degrading en zyme indoleamine 2,3-dioxygenase. In contrast to IFN-gamma-induced eff ects, the activity of other cytokines, such as interleukin (IL)-1, IL- 2 and IL-6, is not influenced by heparin. The possible mechanism of he parin-induced inhibition of IFN-gamma is discussed.