Ganglioside and lipid composition of bulk-isolated rat and bovine oligodendroglia

We have examined the ganglioside composition of 30-day and 60-day postnatal rat oligodendroglia, adult bovine oligodendroglia, gray matter, white matter, and myelin and also the total lipid composition of the oligodendroglial preparations. The ganglioside patterns of rat and bovine oligodendroglia, as previously found for human oligodendroglia, were more complex than those of myelin. These data indicate that oligodendroglial perikarya can synthesize many brain type gangliosides, not all of which are incorporated into the compact myelin. Alternatively, the ganglioside composition of myelin may be altered in situ by the myelin-associated neuraminidase. In these two species, as in human, GM4 appears specific to oligodendroglia and myelin, while GD3 and GM3 are enriched in oligodendroglia but not myelin. In bovine oligodendrocytes GD3 is the major ganglioside. The total lipid concentration, as well as the percentage of cholesterol, sphingomyelin, phosphatidylinositol, and phosphatidylserine, differ for 30- and 60-day-old rat oligodendroglia and may be developmentally correlated with changes in myelin composition during myelinogenesis. There are also marked differences in the lipid composition of bovine oligodendroglia compared to rat oligodendroglia, with the former having more galactolipid and less ethanolamine phosphoglycerides.     

Synthesis of gangliosides by cultured oligodendrocytes

Gangliosides are enriched in the nervous system compared to other tissues. The synthesis of gangliosides by monolayer cultures of isolated oligodendrocytes has not previously been investigated. Cells were labeled with [³H]galactose at preselected times and gangliosides isolated by phase partition, purified, and identified by chromatography. Cultured oligodendrocytes showed selectivity in their synthesis of gangliosides, which was expressed in the type of ganglioside synthesized as well as in the change of incorporation over time in culture. For the first ten days, there was very little incorporation of [³H]galactose in gangliosides, but this was followed by a stimulation of uptake for G_M3, G_M1/G_D3, and G_D1 gangliosides, reaching a maximum after approximately 25–30 days in vitro. There was little incorporation into G_M2 or trisialogangliosides throughout the life of the cultures. Since oligodendrocytes synthesize extensive membranes during this period, one may speculate that the de novo-synthesized gangliosides are used for membranes.     

Effect of gangliosides secreted by ascites hepatoma 22a cells on intensity of protein synthesis in these cells and on their sensitivity to indocarb

Bulletin of Experimental Biology and Medicine -     

Role of Gangliosides in Active Immunotherapy with Melanoma Vaccine

Among various tumor associated cell surface antigens, gangliosides, the glycosphingolipids that contain sialic acids, offer a variety of epitopes, some of which are preferentially expressed on melanoma cells. These surface components of the bilayered lipid membrane of tumor cells are the targets of active immunotherapy with melanoma vaccine. Purified gangliosides in aqueous solution form micelles and, at high density, form lactones. Their antigenic expression (physical conformation and orientation) on the cell surface is governed by the nature of the sphingosine and the fatty acids they contain. Evidence is accruing to show that the nature of the fatty acid moiety of gangliosides differs in normal and neoplastic cells. Gangliosides per se are not immunogenic and require extrinsic adjuvanticity. Preparation of a melanoma cell vaccine for active immunotherapy requires an understanding of the ganglioside profile of melanoma, the ganglioside-associated heterogeneity of melanoma, and the role of shed melanoma gangliosides in the immunosuppression of cell mediated and humoral immunity. In addition, the role of some of the anti-ganglioside antibodies in the elimination of shed gangliosides, the cytotoxic killing of tumor cells, as well as in the down-regulation of lymphocyte functions must be considered in the formulation of vaccine. Different strategies for augmenting the immunogenicity of melanoma associated gangliosides with melanoma vaccine are evaluated.     

The presence of foetal ganglioside antigens 3′-IsoLM1 and 3′6′-IsoLD1 in both glioma tissue and surrounding areas from human brain

Summary Glioma-associated gangliosides, in particular the expression of foetal gangliosides 3′-isoLM1 and 3′6′-isoLD1, have been investigated in biopsies from 44 patients with astrocytoma grade II, anaplastic astrocytoma, anaplastic oligodendrogliomas, oligodendrogliomas, and glioblastoma multiforme. The total ganglioside content decreased in proportion to the estimated number of tumour cells present in the biopsy. Ganglioside GD3 was increased in 17 of the tumour tissues and in 6 of the surrounding area specimens. In agreement with our previous studies, tumour specimens contained the lactoseries ganglioside 3′-isoLM1 and, as demonstrated for the first time, the disialylated form of the ganglioside, 3′6′-isoLD1. These gangliosides are in normal brain tissue restricted to the developmental period. Most frequent was the expression of ganglioside 3′-isoLM1 which was detected in 92% of the tumour specimens in concentrations varying between just detectable amounts to 13 nmol/g wet weight. In the area surrounding the macroscopic tumour tissue 78% of the specimens expressed 3′-isoLM1 and the values varied between just detectable amounts to 24 nmol/g wet weight. Ganglioside 3′6′-isoLD1 was found in 47% of the tumour biopsies and in only 17% of the specimens taken outside macroscopic tumour tissue. The values varied between non-detectable amounts to 40 nmol/g wet weight of tissue. The expression of 3′-isoLM1 correlated significantly (p<0.01) to malignancy grade. For 3′6′-isoLD1 a significant (p<0.05) difference was found between tomour and surrounding tissue. Likewise, 3′6′-isoLD1 correlated significantly (p<0.05) to malignancy grade. The correlation between 3′-isoLM1 and 3′6′-isoLD1 to malignancy grade and the frequent expression of these gangliosides both in the tumour itself and in its surrounding area should encourage additional studies concerning their biological role in tumour disease.     

呼吸系疾病患者血清神经节苷脂与癌胚抗原

目的:研究呼吸系疾病患者血清神经节苷脂(gangliosides,GLS)与癌胚抗原(car-cinoembryonicantigen,CEA)含量及意义。方法:测定患者血清GLS、CEA,分组统计分析。结果:恶性肿瘤、结核、肺炎、慢性支气管炎组血清GLS含量分别为(908±300)、(755±316)、(820±294)、(570±147)mg/L;阳性率分别为87·8%、42·8%、61·1%和23·4%。四组血清CEA含量分别为(19·3±20·1)、(10·7±5·6)、(11·7±8·4)和(10·9±9·9)μg/L;阳性率分别为39·1%、20·0%、13·9%和18·8%。恶性肿瘤组中肺癌患者GLS含量及阳性率呈现未分化癌>鳞癌>腺癌,CEA正相反。GLS和(或)CEA阳性在恶性肿瘤组占92·2%,可作肺癌初筛指标;GLS和CEA阳性在恶性肿瘤组占34·8%,在非癌各组总计占5·8%,可作肺癌诊断指标。结论:肺癌患者血清GLS显著增加,对肺癌诊断有一定意义;GLS与CEA联合检测对肺癌诊断可能更有价值。     

体内实验研究神经节苷脂对小鼠迟发型变态反应的影响

目的探讨神经节苷脂对小鼠迟发型变态反应的作用。方法体内利用肿瘤相关抗原皮下注射到小鼠背部皮下，每周一次，连续三周，使小鼠致敏，第四周对小鼠进行激发试验，刺激产生迟发型变态反应，即将表皮郎格罕氏细胞与神经节苷脂和肿瘤相关抗原共同孵育后注射到小鼠后足掌侧，分别于注射后24，48小时测量足掌肿胀程度来评估神经节苷脂对小鼠迟发型变态反应的作用。结果神经节苷脂可降低小鼠足掌肿胀程度，抑制小鼠迟发型变态反应。结论神经节苷脂具有抑制小鼠迟发型变态反应，同时说明神经节苷脂可以抑制表皮郎格罕氏细胞抗原提呈作用。     

Multiple Sclerosis: Cell-Mediated Immunity to Human Brain Gangliosides

Cell-mediated immunity (CMI) to myelin components has been implicated in Multiple Sclerosis (MS) pathogenesis: two targets were suggested, Myelin Basic Protein with controversial results and, more recently, gangliosides. In order to investigate their possible involvement, we have performed Leukocyte Migration inhibition (LMI) tests in the presence of human brain gangliosides. Thirty nine MS patients (twenty four bcing “definite”, according to McDonald and Halliday's classification), twenty nine patients with Other Neurological Diseases (OND), thirty six patients with Inflammatory diseases (ID) and forty healthy controls were tested. MS patients wcrc divided into two groups, depending on the clinical stage of the disease.

The mean migration inhibiton percentage of the MS-attack group was found to be significantly different from the four others (p < 0.01) (24.4 ± 16.2 versus 10.9 ± 8.5 in MS without attack, 4.4 ± 12.9 in OND. 3.9 ± 13.9 in ID and 11.1 ± 12.1 in healthy subjects). LMI to gangliosides is therefore significantly increased during the attack stage in MS. These results support the notion of a Delayed Type Hypersensitiv-ity to these glycolipids during the active stage of the disease.