Chemokine receptors in chronic obstructive pulmonary disease (COPD)

Abstract

Chronic obstructive pulmonary disease (COPD) is a debilitating disease characterized by recurrent episodes of leukocyte infiltration in the lung parenchyma causing progressive pulmonary tissue damage and loss of function. Recruitment of neutrophils and CD8+ T cells is linked to disease progression and is under control of chemotactic mediators produced in the inflamed COPD lung. Recent progress in elucidation of the molecular mechanisms that regulate migration of inflammatory cells into the lung has revealed interesting novel targets for therapeutic intervention in this disease. Chemokine receptors CXCR1 and CXCR2 expressed on neutrophils and CXCR3 expressed on CD8+ T cells have been identified as potential therapeutic targets to prevent recruitment of pathogenic cells into the inflamed lung. However, the observation that chemokine receptors are also expressed and functional on various types of lung resident cells including epithelial and smooth muscle cells has raised new questions on the role played by chemokine receptors in COPD. These new findings suggest that chemokine receptor signalling could contribute to the adaptive response of lung tissue resident cells to the microenvironmental changes induced by inflammation. Thus, investigation of the role played by chemokine receptors in development of COPD remains a fertile area of research. Nevertheless, validation of chemokine receptor targets in COPD has proven a difficult challenge given the lack of predictive animal models of the disease and the still poorly defined etiology and pathogenesis.