Nie Li, Xiang Ruolan, Zhou Weixun, Lu Bao, Cheng Deyun, Gao Jinming
Department of Respiratory Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China.
Respir Res. 2008 Dec 16;9(1):82. doi: 10.1186/1465-9921-9-82.
CD8+ T cells may participate in cigarette smoke (CS) induced-lung inflammation in mice. CXCL10/IP-10 (IFNgamma-inducible protein 10) and CXCL9/Mig (monokine induced by IFN-gamma) are up-regulated in CS-induced lung injury and may attract T-cell recruitment to the lung. These chemokines together with CXCL11/ITAC (IFN-inducible T-cell alpha chemoattractant) are ligands for the chemokine receptor CXCR3 which is preferentially expressed chiefly in activated CD8+ T cells. The purpose of this investigation was to study the contribution of CXCR3 to acute lung inflammation induced by CS using CXCR3 knockout (KO) mice.
Mice (n = 8 per group) were placed in a closed plastic box connected to a smoke generator and were exposed whole body to the tobacco smoke of five cigarettes four times a day for three days. Lung pathological changes, expression of inflammatory mediators in bronchoalveolar lavage (BAL) fluid and lungs at mRNA and protein levels, and lung infiltration of CD8+ T cells were compared between CXCR3-/- mice and wild type (WT) mice.
Compared with the WT littermates, CXCR3 KO mice showed less CS-induced lung inflammation as evidenced by less infiltration of inflammatory cells in airways and lung tissue, particularly fewer CD8+ T cells, lower levels of IFNgamma and CXCR3 ligands (particularly CXCL10).
Our findings show that CXCR3 is important in promoting CD8+ T cell recruitment and in initiating IFNgamma and CXCL10 release following CS exposure. CXCR3 may represent a promising therapeutic target for acute lung inflammation induced by CS.
CD8 + T细胞可能参与香烟烟雾（CS）诱导的小鼠肺部炎症。CXCL10/IP - 10（γ干扰素诱导蛋白10）和CXCL9/Mig（γ干扰素诱导的单核因子）在CS诱导的肺损伤中上调，可能吸引T细胞募集至肺。这些趋化因子与CXCL11/ITAC（γ干扰素诱导的T细胞α趋化因子）一起是趋化因子受体CXCR3的配体，CXCR3主要在活化的CD8 + T细胞中优先表达。本研究的目的是使用CXCR3基因敲除（KO）小鼠研究CXCR3对CS诱导的急性肺部炎症的作用。
将小鼠（每组n = 8）置于连接烟雾发生器的封闭塑料盒中，每天4次全身暴露于5支香烟的烟草烟雾中，持续3天。比较CXCR3 - / - 小鼠和野生型（WT）小鼠的肺病理变化、支气管肺泡灌洗（BAL）液和肺中炎症介质在mRNA和蛋白水平的表达以及CD8 + T细胞的肺浸润情况。
与WT同窝小鼠相比，CXCR3 KO小鼠表现出较少的CS诱导的肺部炎症，表现为气道和肺组织中炎症细胞浸润较少，尤其是CD8 + T细胞较少，γ干扰素和CXCR3配体（特别是CXCL10）水平较低。
我们的研究结果表明，CXCR3在促进CD8 + T细胞募集以及CS暴露后启动γ干扰素和CXCL10释放方面很重要。CXCR3可能是CS诱导的急性肺部炎症的一个有前景的治疗靶点。
