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Natural killer cells (NK) demonstrate cytotoxicity against a wide range of cultured cells without prior sensitization, and the sensitivity of many target cells to NK attack is altered by exposure to interferon. The structures on the target cells conferring sensitivity or resistance to NK are not known, but glycolipids are suggested to be related to NK susceptibility. To determine possible relationships between target cell glycolipids and NK cytolysis, the effects of human beta-interferon (IFN) on the neutral glycolipid composition and sensitivity to NK cytolysis of cultured cells from four human gliomas and two fetal brains were analyzed. Compared to MOLT-4 and Raji cells all six neural cell lines were quite resistant to NK, and IFN slightly increased this resistance. IFN also caused increases in the amounts of non-hydroxy fatty acid cerebroside, ceramide trihexoside, asialo-GM1, asialo-GM2 and globoside. Increased molar proportions of ceramide tri- and tetra-saccharides occurred in the two glioma lines which had the greatest increases in NK resistance following IFN exposure. It is concluded that neutral glycolipids may play a role in the mechanisms responsible for resistance of some glioma cells to NK cytolysis.

Marked changes in ganglioside composition occur during brain development and in cultured neurons concomitant with differentiation, and maximum ganglioside synthesis occurs during neuronal maturation and synaptogenesis. These findings indicate that gangliosides probably play an important role in brain development. In this study the effects of parenterally administered l -cycloserine (an inhibitor of sphingosine synthesis) on gangliosides during the period of rapid neonatal brain growth in mice were studied. Two groups of mice (saline control and l -cycloserine—20 mg/kg/day) were treated for 8 or 16 days, starting at postnatal day 6, and sacrificed at 14, 22, 32, 62 or 110 days of age. Undernourished controls were also sacrificed at the same times. Body and cerebral weights in the l -cycloserine group were less than those of saline control animals at early ages, but the l -cycloserine animals did not show sparing of cerebral weight in relation to body weight as did the undernourished controls. Compared to saline control animals the l -cycloserine group had significantly less total lipid extract and nonlipid residue over all age groups. Animals treated with l -cycloserine had less total ganglioside NeuNAc per hemisphere, but normal concentrations on a fresh weight basis. Both groups had identical ganglioside patterns. These results indicate that although l -cycloserine does affect some aspects of brain development, it is not useful as a selective inhibitor of ganglioside synthesis in neonatal ICR Swiss Webster mice treated with a dose equivalent to the LD-17. Its value in modifying ganglioside synthesis should be viewed with caution.

This investigation tested the hypothesis that the growth inhibiting effects of human beta-interferon on cultured human glioma cells involves changes in the ganglioside composition of these cells. Four cell lines derived from human malignant gliomas (12-18, U-251 MG, I29-A, 7-24) and two lines from human fetal brain (CHI, CHII) were cultured in the presence and in the absence of human beta-interferon (HuIFN-beta), 1,000 units per ml medium for three days before harvesting. Human beta-interferon had an inhibitory effect on growth of glioma but not fetal brain cells. Total ganglioside sialic acid for all cell lines ranged between 3.5 and 13.8 micrograms/10(7) cells (0.6-3.9 micrograms/mg protein). No distinct difference in the amount of total ganglioside per cell was observed between neoplastic and non-neoplastic cells, but the latter had more ganglioside per mg total protein. All cell lines displayed different patterns of gangliosides determined by high performance thin layer chromatography, but there was no distinct difference between glioma and fetal brain cells. Human beta-interferon increased the total amount of ganglioside per cell in one fetal brain and two glioma lines, but on a protein basis in only one glioma cell line (I29-A); HuIFN-beta had only minor effects on ganglioside patterns. There was a slight shift towards a greater proportion of structurally simpler gangliosides in both fetal brain and two glioma cell lines exposed to HuIFN-beta, but the reverse occurred in glioma U-251 MG. None of these changes strongly correlated with the degree of growth inhibition due to HuIFN-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

Ganglioside patterns were quantitated for brains of bullfrog (Rana catesbiana) at three stages of metamorphosis and adult. At each stage nine gangliosides were identified by mobility on silica gel thin-layer chromatograms, and quantitated on the basis of sialic acid content. A single band with chromatographic mobility close to that of GD2, and doublets close to GT1b and GQ were quantitatively the major ones (over 16% each). Doublets close to GM1 and GD1b and a single band slightly behind GD1a made up 5–10% each. A doublet comigrating with GM3, and bands close to GM2 (trace) and GD3 were present in smaller amounts. The only developmental trend was a slight increase in the proportion of the band close to GD3 from 2.4% (early prometamorphic phase) to 9.1% (adult). This suggests that changes in the regenerative capacity of frog nervous tissues during metamorphosis are due to changes other than ganglioside composition.