Microglial activation by serum factors

小胶质细胞是中枢神经系统（CMS）的常驻免疫细胞。他们一直 涉及许多急性和慢性神经系统疾病，包括创伤、中风和多发性硬化症， 疾病。在CNS损伤后，小胶质细胞迅速活化。通过释放生物活性物质 例如细胞因子激活的小胶质细胞可以对 神经元直到最近，研究主要集中在细胞因子激活小胶质细胞。这些强效 肽引起广泛的反应，包括增殖、运动和细胞因子释放本身。 然而，在细胞因子能够激活小胶质细胞之前，它们需要被诱导、合成和 从邻近的细胞中释放出来。据报道，CNS损伤后小胶质细胞的快速活化导致了 问：是否有其他更快的小胶质细胞激活剂？一组候选者是血清因子 （SF）。在与心脑血管损伤相关的损伤过程中，SF渗漏到CNS实质中。 屏障，如创伤、中风和多发性硬化症。因此，血清因子可以作为 损伤的信号，并激活小胶质细胞，而不需要中介，细胞因子产生“接力” 细胞我们假设血清因子（SF）代表了小胶质细胞激活的“捷径”。基于 最近发表的报告和我们的初步研究结果，我们建议检查血清的影响， 凝血酶、溶血磷脂酸和1-磷酸鞘氨醇对小胶质细胞活化的影响。使用 分子、免疫学和成像技术将解决以下问题：1.确定 体外SF激活小胶质细胞的细胞后果。2.确定信号转导 参与SF介导的小胶质细胞体外活化的机制。S.确定细胞后果 在视网膜外植体原位培养模型中，SF激活小胶质细胞。 在许多病理事件中，SF在第一阶段细胞因子之前很久就立即作用于小胶质细胞 会影响小胶质细胞的行为每一种受体或信号转导机制的确定 可能构成CNS损伤治疗干预的新靶点， 血脑屏障的破坏，如创伤、多发性硬化症或中风。

Microglial cells are the resident immune cells of the central nervous system (CMS). They have been implicated in many acute and chronic neurological diseases, including trauma, stroke and multiple scler- osis. Upon CNS injury microglial cells are rapidly activated. Through the release of bioactive substances such as cytokines activated microglial cells can exert powerful toxic as well as protective effects on neurons. Until recently, research has mainly focused on microglial activation by cytokines. These potent peptides elicit a broad range of responses, including proliferation, motility and cytokine release itself. Nevertheless, before cytokines can activate microglia, they need to be induced, synthe- sized and released from neighboring cells. The reported rapid activation of microglia after CNS injury, leads to the question: Are there other, faster acting microglial activators? One group of candidates are serum factors (SFs). SFs leak into the CNS parenchyma during insults associated with impairment of the bood-brain- barrier, such as trauma, stroke, andmultiple sclerosis. Serum factors therefore could serve as immediate signals of injury and activate microglial cells without the need of intermediary, cytokine- producing "relay" cells. We hypothesize that serum factors (SF) represent a "short-cut" to microglial activation. Based on recently published reports and our preliminary findings, we propose to examine the effects of the serum factors thrombin, lysopho- sphatidic acid and sphingosine-1-phospate on microglial Activation. Using molecular, immunological and imaging techniques the following issues will be addres- sed: 1. Determine the cellular consequences of microglial activation by SFs in vitro. 2.Determine the signal transduction mechanisms involved in SF-mediated microglial activation in vitro. S.Determine the cellular consequences of microglial activation by SFs in a retina explant culture model in situ. In many pathological events SFs act immediately on microglial cells, long before first-phase cytokines could influence microglial behavior. Each of the receptors or signal transduction mechanisms identified may constitute a new target for therapeutic intervention in CNS injuries, which are accompanied by the break down of the blood-brain-barrier, such as trauma, multiple sclerosis or stroke.