Recruitment of blood fibrocytes during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4 dependent pathway

Abstract

Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial fibrosis. The chronic course of COPD is worsened by recurrent acute exacerbations. The aims of the study were to evaluate and understand the recruitment of blood fibrocytes in COPD patients during exacerbation. Methods: Using flow cytometry, we quantified circulating fibrocytes and characterized their chemokine receptors expression in 48 COPD patients during acute exacerbation (V1 COPD), two months after (V2 COPD), and 38 control subjects. The role of the chemokines CXCL12 and CCL11 in fibrocyte migration was investigated by a modified chemotaxis assay. Patients were followed for up to 3 years after V1. Results: We demonstrated a significant increased number of circulating fibrocytes in V1 COPD as compared to control subjects. The number of circulating fibrocytes decreased in V2 COPD. A high percentage of circulating fibrocytes during exacerbation was associated with increased risk of death. The percentage of fibrocytes at V2 was negatively correlated to FEV1, FVC, FEV1/FVC, TLCO and PaO 2 . Fibrocytes expressed in particular CXCR4 and CCR3, the chemokines receptors for CXCL12 and CCL11, respectively. Fibrocytes from V1 COPD had increased chemotactic migration in response to CXCL12 but not to CCL11 as compared to that from control subjects. Plerixafor, a CXCR4 antagonist, decreased fibrocyte migration to plasma of exacerbating COPD patients. Conclusion: Blood fibrocytes are recruited during COPD exacerbations and related to mortality and low lung function. The CXCL12/CXCR4 axis is involved in fibrocyte recruitment (“Firebrob” study; ClinicalTrials NCT01196832).