Upregulation of complement inhibitors in association with vulnerable cells following contusion-induced spinal cord injury
Upregulation of complement inhibitors in association with vulnerable cells following contusion-induced spinal cord injury
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DOI：
10.1089/neu.2005.22.382
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发表时间：
2005-03-01
影响因子：
4.2
通讯作者：
Robert, S
中科院分区：
文献类型：
--
作者：
Anderson, AJ;Najbauer, J;Robert, S
我们之前已经使用纽约大学（NYU）的减重撞击器描述了急性挫伤脊髓损伤后经典、替代和终末补体级联通路的激活。在本研究中，我们在相同的实验模式下研究了补体级联蛋白调节因子、因子H （FH）和聚簇素的诱导。用12.5 mm和50 mm的撞击器对成年大鼠脊髓进行轻、重度损伤。在伤后1、7和42天对对照组和损伤动物的脊髓进行评估。免疫细胞化学显示，在所有三个时间点，损伤脊髓中FH和聚集素阳性细胞的染色数量和强度均显著增加，在损伤后1天和42天观察到最高的增加。在神经元和少突胶质细胞中观察到FH和clusterin阳性细胞。在损伤部位的喙侧和尾侧均检测到表达增加，后者的距离可达20 mm。损伤诱导的这些蛋白上调的确切生物学意义仍有待确定。然而，FH和clusterin是针对促炎级联的上游（FH）和下游（clusterin）分子的补体活性的有效调节剂，这可能对防止损伤脊髓的“失控”炎症反应至关重要。
We have previously described the activation of the classical, alternative, and terminal complement cascade pathways after acute contusion spinal cord injury using the New York University (NYU) weight-drop impactor. In the present study, we examined the induction of protein regulators of the complement cascade, factor H (FH), and clusterin, in the same experimental paradigm. The spinal cord of laminectornized adult rats was subjected to mild or severe injury using impactor weight-drop heights of 12.5 and 50 mm, respectively. The spinal cords of control and injured animals were evaluated at 1, 7, and 42 days after injury. Immunocytochernistry revealed a robust increase in the numbers and intensity of staining of FH, and clusterin-positive cells in the injured cord at all three time points, with the highest increases observed at 1 and 42 days after injury. FH and clusterin-positive cells were observed among neurons as well as oligodendrocytes. The increased expression was detected both rostrally and caudally from the injury site, in the latter case at distances up to 20 mm. The precise biological significance of injury-induced upregulation of these proteins remains to be determined. However, FH and clusterin are potent regulators of complement activity targeting upstream (FH) and downstream (clusterin) molecules of the pro-inflammatory cascade, which could be of vital importance in preventing a "runaway" inflammatory reaction in the injured spinal cord.