RRC ID 62889
著者 Hijioka M, Futokoro R, Ohto-Nakanishi T, Nakanishi H, Katsuki H, Kitamura Y.
タイトル Microglia-released leukotriene B4 promotes neutrophil infiltration and microglial activation following intracerebral hemorrhage.
ジャーナル Int Immunopharmacol
Abstract Intracerebral hemorrhage (ICH) from blood vessel rupture results in parenchymal hematoma formation and neuroinflammation, ultimately leading to neurodegeneration. Several lines of evidence suggest that the severity of ICH-induced neural damage is exacerbated by infiltration of T-cells, monocytes, and especially neutrophils into the hematoma. Neutrophil migration is regulated by chemokines, formyl peptides, and leukotriene B4 (LTB4), a metabolite of arachidonic acid. In this study, we demonstrate that LTB4 is a key signaling factor promoting microglial activity and leukocyte infiltration into hematoma and thus a potentially critical determinant of ICH pathogenesis and clinical outcome. Lipidomic analysis revealed markedly increased LTB4 concentration in the hematoma-containing brain tissues 6-24 h after experimental ICH in mice. Expression of 5-lipoxygenase, a rate-limiting enzyme for LTB4 production, was upregulated in activated microglia and neutrophils within the hematoma following ICH. Treatment of cultured BV-2 microglia with thrombin, which is abundant in hematoma, promoted activation, proinflammatory cytokine expression, and LTB4 secretion. Further, conditioned medium from thrombin-stimulated BV-2 cells potentiated the transwell migration of neutrophil-like cells, a response blocked by a LTB4 receptor antagonist. These results suggest that arachidonic acid conversion to LTB4 following ICH contributes to neuroinflammation and ensuing neural tissue damage by inducing microglial activation and neutrophil recruitment.
巻・号 85
ページ 106678
公開日 2020-8-1
DOI 10.1016/j.intimp.2020.106678
PII S1567-5769(20)30284-8
PMID 32544870
MeSH Animals Brain / immunology Cell Line Cerebral Hemorrhage / immunology* Cytokines / genetics Humans Leukotriene B4 / immunology* Male Mice, Inbred C57BL Microglia / immunology* Neutrophil Infiltration*
IF 3.943
リソース情報
ヒト・動物細胞 HL-60(RCB3683)