title: Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is characterized by peribronchial fibrosis. The chronic course of COPD is worsened by recurrent acute exacerbations.
  
  
  OBJECTIVE
  The aim of the study was to evaluate the recruitment of blood fibrocytes in patients with COPD during exacerbations and, subsequently, to identify potential mechanisms implicated in such recruitment.
  
  
  METHODS
  Using flow cytometry, we quantified circulating fibrocytes and characterized their chemokine receptor expression in 54 patients with COPD examined during an acute exacerbation (V1) and 2 months afterward (V2) and in 40 control subjects. The role of the chemokines CXCL12 and CCL11 in fibrocyte migration was investigated by using a chemotaxis assay. Patients were followed for up to 3 years after V1.
  
  
  RESULTS
  We demonstrated a significantly increased number of circulating fibrocytes at V1 compared with control subjects. The number of circulating fibrocytes decreased at V2. A high percentage of circulating fibrocytes during exacerbation was associated with increased risk of death. The percentage of fibrocytes at V2 was negatively correlated with FEV1, forced vital capacity, FEV1/forced vital capacity ratio, transfer lung capacity of carbon monoxide, and Pao2. Fibrocytes highly expressed CXCR4 and CCR3, the chemokine receptors for CXCL12 and CCL11, respectively. Fibrocytes collected from patients with COPD at V1 had increased chemotactic migration in response to CXCL12 but not to CCL11 compared with those from control subjects. Plerixafor, a CXCR4 antagonist, decreased fibrocyte migration to plasma from patients with exacerbating COPD.
  
  
  CONCLUSIONS
  Blood fibrocytes are recruited during COPD exacerbations and related to mortality and low lung function. The CXCL12/CXCR4 axis is involved in such fibrocyte recruitment (Firebrob study; ClinicalTrials NCT01196832).
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France. Electronic address: isabelle.dupin@u-bordeaux.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dupin
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Allard
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Annaig
authors.initials: A
authors.lastname: Ozier
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Maurat
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France.
authors.forename: Olga
authors.initials: O
authors.lastname: Ousova
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Delbrel
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Trian
authors.affiliation: CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Hoang-Nam
authors.initials: HN
authors.lastname: Bui
authors.affiliation: CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Dromer
authors.affiliation: CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Guisset
authors.affiliation: CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Blanchard
authors.affiliation: CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Hilbert
authors.affiliation: CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vargas
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Thumerel
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Girodet
authors.affiliation: Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, Bordeaux, France; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France. Electronic address: patrick.berger@u-bordeaux.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Berger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D054413:Chemokine CCL11 / Q000097:blood; D054377:Chemokine CXCL12 / Q000097:blood*; D002633:Chemotaxis; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000401:mortality / Q000503:physiopathology*; D054397:Receptors, CCR3 / Q000097:blood; D019718:Receptors, CXCR4 / Q000097:blood*
chemical_list: D015415:Biomarkers; C515456:CCL11 protein, human; C515350:CCR3 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054413:Chemokine CCL11; D054377:Chemokine CXCL12; D054397:Receptors, CCR3; D019718:Receptors, CXCR4
keywords: Chronic obstructive pulmonary disease; chemotaxis; fibrocyte; lung function; mortality