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

Most CNS pathologies are accompanied by the occurrence of activated, phagoc ytic microglial cells. We intended to investigate whether (1) isolated micr oglial cells removed from the CNS cytokine network sustain their capacity t o acquire an activated phenotype when challenged with cellular or noncellul ar debris; and (2) different substrates lead to different patterns of micro glial activation. It; was observed that although removed from their usual s urroundings microglial cells preserve their ability to transform to an amoe boid morphology, form multinucleated giant cells, and enhance their express ion 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. Interfer on-p (IFN-p), a substance clinically used in the treatment of the relapsing -remitting form of multiple sclerosis, was shown to inhibit the phagocytosi s-induced upregulation of MHC-class II. In summary, phagocytic microglial c ells are independent from the CNS cytokine network in their transition from a resting to an activated phenotype; and different cellular substrates, re gardless whether they are of neuronal, glial, or even malignant origin, res ult in similar morphological and functional changes. (C) 2000 Wiley-Liss, I nc.