放射線肺臓炎の発生機序に関する研究 : マウス全肺照射後の接着分子 ICAM-1,VCAM-1,P-selectinの発現の変化について

放射線肺臓炎の発症における接着分子の関与を解明するために, C57BL/6Jマウスの全胸郭に電子線を用いて1回照射を行い, 経時的に肺を摘出し, 肺組織中の接着分子mRNAの発現を Northern blot 法により定量した。12Gy1回照射後のICAM-1 mRNAは4時間後に非照射群と比較して42% (p<0.05), 24時間後には76% (p<0.01), 48時間後には51% (p<0.05) の有意な増加を認めた。1週間後以降8週までには有意な変化はみられなかった。VCAM-1 mRNAはICAM-1よりやや早く12時間後に49% (p<0.01) のピークを有する発現の増加を認めた。1週間後にも25% (p<0.05) と有意な増加を認めた。P-selectin mRNA は12時間後に59% (p<0.05) と一過性の発現増加を認めた。また, ICAM-1の発現と放射線量との関係の検討では, ICAM-1は3Gyの低線量から発現が誘導され, 24Gyまでは線量依存性に発現量が増加した。これらの一過性ではあるが有意なICAM-1, VCAM-1, P-selectinの発現増加は, in vivo における電離放射線照射後の肺の遺伝子レベルの変化として報告されている中では最も早いもののひとつであり, その後に続く放射線肺臓炎の発症に関与していると考えられた。 / To investigate the role of the adhesion molecules in the pathogenesis of the radiation pneumonitis, we quantified the mRNA expression of the adhesion molecules in the lung by Northern blot method following whole thorax irradiation to C57BL/6J mice. After irradition of 12Gy to the whole thorax, there were increase of mRNA for ICAM-1 by 42% at 4 hours (p<0.05), 76% at 24hours (p<0.01) and 51% at 48hours (p<0.05) compared with controls. And it returned to control level at 1 week. No significant change was observed thereafter until 8 weeks. The expression of VCAM-1 mRNA were also increased by 49% (p<0.01) at 12hours and were still increased by 25% at 1 week. P-selectin mRNA were transiently increased by 59% at 12hours. We examined the relationship between the ICAM-1 induction and the radiation dose, and found that ICAM-1 expression was increased by 3Gy of irradiation and it was increased in radiation dose dependent manner up to 24Gy. These early inductions of mRNA for ICAM-1, VCAM-1 and P-selectin in mice lungs following thoracic irradiation were transient but significant, and they were one of the most immediate change reported in vivo. It is suggested that these adhesion molecules are possibly related to the pathogenesis of the radiation pneumonitis.