Attenuation of acute lung inflammation induced by cigarette smoke in CXCR3 knockout mice.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Nie
Li
L
Department of Respiratory Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China. bywaters@163.com
Xiang
Ruolan
R
Zhou
Weixun
W
Lu
Bao
B
Cheng
Deyun
D
Gao
Jinming
J
D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D012906:Smoke; D014028:Tobacco Smoke Pollution
C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D012906:Smoke; D014028:Tobacco Smoke Pollution