The LTB4-BLT1 Axis Mediates Neutrophil Infiltration and Secondary Injury in Experimental Spinal Cord Injury
The LTB4-BLT1 Axis Mediates Neutrophil Infiltration and Secondary Injury in Experimental Spinal Cord Injury
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DOI：
10.2353/ajpath.2010.090839
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发表时间：
2010-05-01
影响因子：
6
通讯作者：
Okada, Seiji
中科院分区：
文献类型：
--
作者：
Saiwai, Hirokazu;Ohkawa, Yasuyuki;Okada, Seiji
中枢神经系统的创伤性损伤诱导炎症;然而，这种炎症的作用是有争议的。精确分析炎症细胞对于更好地理解神经损伤后的炎症机制非常重要。在这里，我们证明了白三烯B4在介导脊髓损伤后白细胞浸润中起着重要作用。使用流式细胞术，我们发现，中性粒细胞和单核细胞/巨噬细胞浸润达到峰值后12小时损伤，并显着抑制在白三烯B4受体1敲除小鼠。在用白三烯B4受体拮抗剂处理的小鼠中观察到类似的发现。此外，通过用细胞分选仪分离每个炎性细胞亚群，并进行定量逆转录-PCR，我们证明了更高表达的亚群（即白细胞介素6和1 β、肿瘤坏死因子-α和FasL）对炎症反应和神经细胞凋亡的个体贡献。抑制白三烯B4可抑制损伤后的白细胞浸润，从而减轻炎症反应，保留白色物质，减少神经细胞凋亡，并诱导更好的功能恢复。这些发现首次证实了白三烯B4通过放大白细胞浸润参与脊髓损伤的发病机制，并为创伤性脊髓损伤提供了潜在的治疗策略。(Am J Pathol 2010，176：2352-2366 DOI：10.2353/ajpath.2010.090839）
Traumatic injury in the central nervous system induces inflammation; however, the role of this inflammation is controversial. Precise analysis of the inflammatory cells is important to gain a better understanding of the inflammatory machinery in response to neural injury. Here, we demonstrated that leukotriene B4 plays a significant role in mediating leukocyte infiltration after spinal cord injury. Using flow cytometry, we revealed that neutrophil and monocyte/macrophage infiltration peaked 12 hours after injury and was significantly suppressed in leukotriene B4 receptor 1 knockout mice. Similar findings were observed in mice treated with a leukotriene B4 receptor antagonist. Further, by isolating each inflammatory cell subset with a cell sorter, and performing quantitative reverse transcription-PCR, we demonstrated the individual contributions of more highly expressed subsets, ie, interleukins 6 and 1 beta, tumor necrosis factor-alpha, and FasL, to the inflammatory reaction and neural apoptosis. Inhibition of leukotriene B4 suppressed leukocyte infiltration after injury, thereby attenuating the inflammatory reaction, sparing the white matter, and reducing neural apoptosis, as well as inducing better functional recovery. These findings are the first to demonstrate that leukotriene B4 is involved in the pathogenesis of spinal cord injury through the amplification of leukocyte infiltration, and provide a potential therapeutic strategy for traumatic spinal cord injury. (Am J Pathol 2010, 176:2352-2366 DOI: 10.2353/ajpath.2010.090839)