Research

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

Li Nie^1,2* , Ruolan Xiang^3* , Weixun Zhou^4* , Bao Lu⁵ , Deyun Cheng² and Jinming Gao¹

¹  Department of Respiratory Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China

²  Department of Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, PR China

³  Department of Pathophysiology, Peking University Health Sciences Center, Beijing 100088, PR China

⁴  Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China

⁵  Ina Sue Perlmutter Laboratory, Division of Pulmonary, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA

author email corresponding author email* Contributed equally

Respiratory Research 2008, 9:82doi:10.1186/1465-9921-9-82

Published:	16 December 2008

Abstract

Background

CD8+ T cells may participate in cigarette smoke (CS) induced-lung inflammation in mice. CXCL10/IP-10 (IFNγ-inducible protein 10) and CXCL9/Mig (monokine induced by IFN-γ) 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 IFNγ and CXCR3 ligands (particularly CXCL10).

Conclusion

Our findings show that CXCR3 is important in promoting CD8+ T cell recruitment and in initiating IFNγ and CXCL10 release following CS exposure. CXCR3 may represent a promising therapeutic target for acute lung inflammation induced by CS.