The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury

Hirokazu Saiwai, Yasuyuki Ohkawa, Hisakata Yamada, Hiromi Kumamaru, Akihito Harada, Hideyuki Okano, Takehiko Yokomizo, Yukihide Iwamoto, Seiji Okada

研究成果: Article

101 引用 (Scopus)

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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 1β, tumor necrosis factor-α, 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.

元の言語English
ページ(範囲)2352-2366
ページ数15
ジャーナルAmerican Journal of Pathology
176
発行部数5
DOI
出版物ステータスPublished - 2010 5

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

フィンガープリント The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    Saiwai, H., Ohkawa, Y., Yamada, H., Kumamaru, H., Harada, A., Okano, H., Yokomizo, T., Iwamoto, Y., & Okada, S. (2010). The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury. American Journal of Pathology, 176(5), 2352-2366. https://doi.org/10.2353/ajpath.2010.090839