敗血症におけるCRTH2の役割を検討した。CRTH2ノックアウト(-/-)マウスは, 敗血症において生存率が上昇し, 腹腔内の細菌数は有意に減少した。CRTH2-/-マウスは, 腹腔内のCXCR2陽性の好中球が増加した。好中球マーカーであるGr-1の抗体や, CXCR2抗体の投与実験の結果, CRTH2-/-マウスの保護的効果の機序にCXCR2陽性の好中球の腹腔内への集積が寄与していた。感染2時間後の末梢好中球のCXCR2プロモーター領域のヒストンH3のアセチル化は, 野生型では低下するが, CRTH2-/-マウスでは低下せず, CXCR2の発現はエピジェネティック制御を受けることが示唆された。
We evaluated the role of CRTH2 using a mice model of polymicrobial sepsis. CRTH2 knockout (-/-) mice were highly resistant to sepis and peritoneal bacterilal load in CRTH2-/- mice was significantly lower as compared to that in wild-type mice.Pharmacological inhibition of Gr-1, a neutrophil marker, and CXCR2 attenuated the protective effects aganist sepsis in CRTH2-/- mice, indicating that CXCR2-expressing neutrophils play protective roles in CRTH2-/- mice in this sepsis model. Moreover, acetylation of histone H3 at CXCR2 promoter in perippheral neutrophils was reduced 2 h after the surgery in wild-type neutrophils, while that in CRTH2-/- mice was not reduced 2 h after the surgery, suggesting that CXCR2 expression is regulated by epigenetic change.
|
