Phagocytosis of neuronal or glial debris by microglial cells: upregulation of MHC class II expression and multinuclear giant cell formation in vitro

Most CNS pathologies are accompanied by the occurrence of activated, phagocytic microglial cells. We intended to investigate whether (1) isolated microglial cells removed from the CNS cytokine network sustain their capacity to acquire an activated phenotype when challenged with cellular or noncellular debris; and (2) different substrates lead to different patterns of microglial activation. It was observed that although removed from their usual surroundings microglial cells preserve their ability to transform to an amoeboid morphology, form multinucleated giant cells, and enhance their expression of MHC class II when exposed to membranes of neuronal or glial origin. Furthermore, cellular substrates derived from primary hippocampal neuronal cultures, neuroblastic cells (B50), or glial cells were all able to induce similar morphological changes and enhanced expression of MHC class II. In contrast, phagocytosis of Latex beads induced an amoeboid morphology but no increase in the expression of immunologically relevant molecules. Interferon-beta (IFN-beta), a substance clinically used in the treatment of the relapsing-remitting form of multiple sclerosis, was shown to inhibit the phagocytosis-induced upregulation of MHC-class II. In summary, phagocytic microglial cells are independent from the CNS cytokine network in their transition from a resting to an activated phenotype; and different cellular substrates, regardless whether they are of neuronal, glial, or even malignant origin, result in similar morphological and functional changes.