Astroglial control of oligodendrocyte survival mediated by PDGF and leukemia inhibitory factor-like protein.
Astroglial control of oligodendrocyte survival mediated by PDGF and leukemia inhibitory factor-like protein.
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发表时间：
1995-07
期刊：
影响因子：
4.6
通讯作者：
A. Gard;M. Burrell;S. Pfeiffer;J. Rudge;W. Williams
中科院分区：
文献类型：
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作者：
A. Gard;M. Burrell;S. Pfeiffer;J. Rudge;W. Williams
在少突胶质细胞谱系中，程序性死亡和延迟这一过程的生长因子的鉴定表明，其他细胞类型提供少突胶质细胞生长因子。为了确定它们的来源，使用从出生后大鼠大脑免疫纯化的少突胶质母细胞的原代培养物来筛选其他培养的神经和非神经细胞类型，以将存活因子释放到定义的含胰岛素培养基中。在非条件培养基中，少突胶质母细胞在经历终末分化为少突胶质细胞后1-2天死亡，如半乳糖苷表达的开始所定义的。在星形胶质细胞的条件培养基中，与其他测试的细胞类型不同，分化的少突胶质细胞在成熟的髓鞘形成状态下存活数周。存活率部分减少免疫吸附的培养基与抗体血小板衍生生长因子和废除免疫吸附与抗体白血病抑制因子。根据相同的标准，存活活性不归因于其他星形胶质细胞产物，睫状神经营养因子和碱性成纤维细胞生长因子。膜超滤分析表明，活性对应于比天然大鼠白血病抑制因子（M（r）= 43 × 10（3））小的热不稳定蛋白（M（r）= 10（-30）× 10（3））。星形胶质细胞刺激比其他已知的少突胶质细胞营养细胞因子（包括睫状神经营养因子、神经营养因子-3和白血病抑制因子本身）有效> 4倍，单独或组合测试，并且与这些试剂相加地促进存活。这些研究结果表明，星形胶质细胞的功能作为少突胶质细胞和少突胶质细胞的存活的旁分泌调节剂，其效果是介导的血小板源性生长因子，然后由一个强大的细胞因子相关的白血病抑制因子。
Programmed death and the identification of growth factors delaying this process in the oligodendrocyte lineage suggest that other cell types provide oligodendrogliotrophins. To determine their source, primary cultures of oligodendroblasts immunopurified from postnatal rat cerebrum were used to screen other cultured neural and non-neural cell types for the release of survival factors into a defined insulin-containing medium. In non-conditioned medium, oligodendroblasts died 1-2 days after undergoing terminal differentiation into oligodendrocytes, as defined by the onset of expression of galactocerebroside. In medium conditioned by astrocytes, unlike the other tested cell types, differentiated oligodendrocytes survived for weeks in a mature myelinogenic state. Survival was partially reduced by immunoabsorption of the medium with antibodies to platelet-derived growth factor and abolished by immunoabsorption with antibodies to leukemia inhibitory factor. By the same criterion, survival activity was not attributed to other astrocytic products, ciliary neurotrophic factor and basic fibroblast growth factor. Membrane ultrafiltration analysis indicated the activity corresponded to heat-labile protein smaller (M(r) = 10(-30) x 10(3)) than native rat leukemia inhibitory factor (M(r) = 43 x 10(3)). The astrocytic stimulus was > 4-fold more efficacious than other known oligodendrogliotrophic cytokines, including ciliary neurotrophic factor, neurotrophin-3 and leukemia inhibitory factor itself, tested singly or in combination, and promoted survival additively with these agents. These findings suggest that astrocytes function as paracrine regulators of oligodendroblast and oligodendrocyte survival and that their effect is mediated initially by platelet-derived growth factor and thereafter by a powerful cytokine related to leukemia inhibitory factor.