Spinal cord injury elicits expression of keratan sulfate proteoglycans by macrophages, reactive microglia, and oligodendrocyte progenitors
Spinal cord injury elicits expression of keratan sulfate proteoglycans by macrophages, reactive microglia, and oligodendrocyte progenitors
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DOI：
10.1523/jneurosci.22-11-04611.2002
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发表时间：
2002-06-01
影响因子：
5.3
通讯作者：
Tuszynski, MH
中科院分区：
文献类型：
--
作者：
Jones, LL;Tuszynski, MH
硫酸角质素蛋白聚糖（KSPG）是细胞外基质分子，其似乎在发育中的脑和脊髓中建立轴突生长的边界。体外研究证实，KSPGs定义了延伸神经突的抑制边界。本研究的目的是探讨脊髓损伤（SCI）后KSPGs是否表达，从而可能作为轴突生长的潜在抑制剂。成年Fischer 344大鼠进行脊髓损伤，并使用5D4单克隆抗KSPG抗体检查KSPG的时空表达。在完整的脊髓中，小胶质细胞亚群在整个白色和灰质中表达5D4-KSPG。损伤后24小时内，5D4-KSPG免疫反应性显著增加，并出现在靠近脊髓病变部位的细胞分布图上，在损伤后3天达到峰值。双重免疫标记显示，5D4-KSPG表达来自病变部位的多种细胞类型，包括反应性小胶质细胞、巨噬细胞和少突胶质祖细胞。星形胶质细胞未被鉴定为5D4-KSPG的来源。在SCI位点的5D4-KSPG的稳健和广泛的产生先于其他脓毒症抑制性蛋白聚糖分子如硫酸软骨素蛋白聚糖的表达。这是第一次证明，KSPGs表达后，SCI的时间和空间的关系，可以发挥早期和重要的作用，在调节轴突生长后SCI。
Keratan sulfate proteoglycans (KSPGs) are extracellular matrix molecules that appear to establish boundaries for axonal growth in the developing brain and spinal cord. In vitro studies confirm that KSPGs define inhibitory boundaries to extending neurites. The aim of the current study was to investigate whether KSPGs are expressed after spinal cord injury (SCI) and thereby might act as potential inhibitors of axonal growth. Adult Fischer 344 rats were subjected to spinal cord lesions, and the temporal and spatial expression of KSPGs was examined using the 5D4 monoclonal anti-KSPG antibody. In the intact spinal cord, a subpopulation of microglia expressed 5D4-KSPG throughout the white and gray matter. Within 24 hr of injury, 5D4-KSPG immunoreactivity substantially increased and appeared on cellular profiles in close proximity to the spinal cord lesion site, peaking 3 d after injury. Double immunolabeling revealed that 5D4-KSPG expression arose from multiple cell types at the lesion site, including reactive microglia, macrophages, and oligodendrocyte progenitors. Astrocytes were not identified as a source of 5D4-KSPG. The robust and extensive production of 5D4-KSPG at sites of SCI precedes the expression of other putatively inhibitory proteoglycan molecules such as chondroitin sulfate proteoglycans. This is the first demonstration that KSPGs are expressed after SCI in a temporal and spatial relationship that could exert an early and important role in modulating axonal growth after SCI.