Isabelle Dupin1, Benoit Allard2, Annaig Ozier3, Elise Maurat2, Olga Ousova2, Eva Delbrel2, Thomas Trian2, Hoang-Nam Bui4, Claire Dromer4, Olivier Guisset4, Elodie Blanchard4, Gilles Hilbert4, Frédéric Vargas4, Matthieu Thumerel3, Roger Marthan3, Pierre-Olivier Girodet3, Patrick Berger5. 1. 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. 2. 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. 3. 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. 4. CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de pneumologie, Services de réanimation médicale, Service de chirurgie thoracique, Pessac, France. 5. 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.
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. CONCLUSION: 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).
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 COPDat 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. CONCLUSION: 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: Daria Barwinska; Houssam Oueini; Christophe Poirier; Marjorie E Albrecht; Natalia V Bogatcheva; Matthew J Justice; Jacob Saliba; Kelly S Schweitzer; Hal E Broxmeyer; Keith L March; Irina Petrache Journal: Am J Physiol Lung Cell Mol Physiol Date: 2018-05-10 Impact factor: 5.464
Authors: Leda M C Coimbra-Campos; Walison N Silva; Ludmila M Baltazar; Pedro A C Costa; Pedro H D M Prazeres; Caroline C Picoli; Alinne C Costa; Beatriz G S Rocha; Gabryella S P Santos; Fabrício M S Oliveira; Mauro C X Pinto; Jaime H Amorim; Vasco A C Azevedo; Danielle G Souza; Remo C Russo; Rodrigo R Resende; Akiva Mintz; Alexander Birbrair Journal: Stem Cell Rev Rep Date: 2021-05-18 Impact factor: 5.739
Authors: Angela Koutsokera; Pierre J Royer; Jean P Antonietti; Andreas Fritz; Christian Benden; John D Aubert; Adrien Tissot; Karine Botturi; Antoine Roux; Martine L Reynaud-Gaubert; Romain Kessler; Claire Dromer; Sacha Mussot; Hervé Mal; Jean-François Mornex; Romain Guillemain; Christiane Knoop; Marcel Dahan; Paola M Soccal; Johanna Claustre; Edouard Sage; Carine Gomez; Antoine Magnan; Christophe Pison; Laurent P Nicod Journal: Front Med (Lausanne) Date: 2017-07-17
Authors: P Heukels; J A C van Hulst; M van Nimwegen; C E Boorsma; B N Melgert; L M van den Toorn; K A T Boomars; M S Wijsenbeek; H Hoogsteden; J H von der Thüsen; R W Hendriks; M Kool; B van den Blink Journal: Respir Res Date: 2018-05-10