Activation of macrophages by recombinant interferon-gamma has no effect on myelin phagocytosis but hinders invasion of nerves in organ culture

Myelin phagocytosis in nerves undergoing Wallerian degeneration was shown to depend on their invasion by non-resident, hematogenous macrophages. This process can be studied in vitro using organ cultures of peripheral nerves exposed to cultured peritoneal macrophages. The present report concerns the effect of recombinant interferon-gamma (rIFN-gamma) on luminol-dependent chemiluminescence, macrophage migration and myelin phagocytosis in organ cultures. Chemiluminescence was activated by rIFN-gamma compared to untreated cells. The macrophage population was capable of activation at any phase of exposure to organ cultures. The engagement of macrophages in myelin phagocytosis, however, varied with the timing of the application of rIFN-gamma. Application from the start of the experiment led to activation of chemiluminescence and also to a complete inhibition of macrophage invasion of the organ culture, thus preventing myelin removal. Application of rIFN-gamma at a later phase of the experiment had no effect on cell invasion and also no detectable effect on the efficiency of myelin phagocytosis. There was no indication that myelin phagocytosis by itself activated chemiluminescence in untreated cultures. Phagocytosis of myelin appears to be a function of macrophages independent of activation causing production of oxygen radicals.