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

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2352-2366
Number of pages15
JournalAmerican Journal of Pathology
Volume176
Issue number5
DOIs
Publication statusPublished - Jan 1 2010

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Leukotriene B4
Neutrophil Infiltration
Spinal Cord Injuries
Leukotriene B4 Receptors
Leukocytes
Wounds and Injuries
Apoptosis
Inflammation
Leukotriene Antagonists
Interleukin-1
Knockout Mice
Reverse Transcription
Monocytes
Interleukin-6
Flow Cytometry
Neutrophils
Central Nervous System
Tumor Necrosis Factor-alpha
Macrophages
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury. / Saiwai, Hirokazu; Ohkawa, Yasuyuki; Yamada, Hisakata; Kumamaru, Hiromi; Harada, Akihito; Okano, Hideyuki; Yokomizo, Takehiko; Iwamoto, Yukihide; Okada, Seiji.

In: American Journal of Pathology, Vol. 176, No. 5, 01.01.2010, p. 2352-2366.

Research output: Contribution to journalArticle

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