J. Mclaurin et al., EFFECT OF TUMOR-NECROSIS-FACTOR-ALPHA AND TUMOR-NECROSIS-FACTOR-BETA ON HUMAN OLIGODENDROCYTES AND NEURONS IN CULTURE, International journal of developmental neuroscience, 13(3-4), 1995, pp. 369-381
Cytokines produced by infiltrating hematogenous cells or by glial cell
s activated during the course of central nervous system disease or tra
uma are implicated as mediators of tissue injury. In this study, we ha
ve assessed the extent and mechanism of injury of human-derived CNS ol
igodendrocytes and neurons in vitro mediated by the cytokines tumor ne
crosis factor alpha and beta and compared these with the tumor necrosi
s factor independent effects mediated by activated CD4(+) T-cells. We
found that activated CD4(+) T-cells, but not tumor necrosis factor alp
ha or beta, could induce significant release of lactate dehydrogenase,
a measure of cell membrane lysis, from oligodendrocytes within 24 hr.
Neither induced DNA fragmentation as measured using a fluorescence ni
ck-end labelling technique. After a more prolonged time period (96 hr)
, tumor necrosis factor a did induce nuclear fragmentation changes in
a significant proportion of oligodendrocytes without increased lactate
dehydrogenase release. The extent of DNA fragmentation was comparable
to that induced by serum deprivation. Tumor necrosis factor beta effe
cts were even more pronounced. In contrast to oligodendrocytes, the ex
tent of DNA fragmentation, assessed by propidium iodide staining, indu
ced in neurons by tumor necrosis factor a was less than that induced b
y serum deprivation. In-situ hybridization studies of human adult glia
l cells in culture indicated that astrocytes, as well as microglia, ca
n express tumor necrosis factor alpha mRNA.