FAS EXPRESSION ON HUMAN FETAL ASTROCYTES WITHOUT SUSCEPTIBILITY TO FAS-MEDIATED CYTOTOXICITY

Fas (APO-1/CD95) is a cell surface receptor, initially identified in l ymphoid cells, but more recently detected in the central nervous syste m under pathologic conditions. Ligation of the fas receptor by fas lig and or by agonist antibodies induces apoptotic cell death in most fas- expressing cells. In the current study, using dissociated cultures of human fetal central nervous system-derived cells, we detected fas expr ession on astrocytes but not on neurons. Such expression differs from our previous results using cultures of human adult central nervous sys tem-derived cells, which demonstrated fas expression on oligodendrocyt es but not on astrocytes; the oligodendrocytes were susceptible to cel l death via this pathway. Using multiple assays of cell death, includi ng nuclear propidium iodide and TUNEL staining to detect nuclear-direc ted injury, cytofluorometric propidium iodide inclusion, and lactate d ehydrogenase release to detect membrane-directed injury, we found that fas ligation, however, did nor induce cell death in the cultured feta l astrocytes. Cytokines that augmented (gamma-interferon) or inhibited (interleukin-4) fetal astrocyte proliferation did not alter fas expre ssion or resistance to fas ligation. Cells obtained immediately ex viv o from human fetal but not from adult central nervous system tissue ex pressed fas; such expression was restricted to astrocytes as assessed by dual-stain immunohistochemistry. The fetal central nervous system c ells did not express fas ligand. Our findings indicate that fas expres sion on central nervous system cells may reflect their state of maturi ty; expression may not, however, always be coupled to susceptibility t o cell death via this pathway. (C) 1998 IBRO. Published by Elsevier Sc ience Ltd.