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

Respir Res. 2008 Dec 16;9(1):82. doi: 10.1186/1465-9921-9-82.

Abstract

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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Mice
  • Mice, Knockout
  • Pneumonia / etiology*
  • Pneumonia / metabolism*
  • Pneumonia / pathology
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / metabolism*
  • Smoke
  • Tobacco Smoke Pollution*

Substances

  • Cxcr3 protein, mouse
  • Receptors, CXCR3
  • Smoke
  • Tobacco Smoke Pollution