Fibrocyte accumulation in bronchi: a cellular hallmark of COPD

• Published in: bioRxiv
• Main Authors: Dupin, Isabelle, Thumerel, Matthieu, Maurat, Elise, Coste, Florence, Begueret, Hugues, Trian, Thomas, Montaudon, Michel, Marthan, Roger, Pierre-Olivier Girodet, Berger, Patrick
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 23.10.2018; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Bone marrow; Bronchus; CD45 antigen; Chronic obstructive pulmonary disease; Computed tomography; Image processing; Lung diseases; Lungs; Obstructive lung disease; Patients; Physiology; Stroma; Surgery; Thoracic surgery; Thorax; lung function; away remodeling; fibrocytes; CT scan; COPD
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/449843

Background: The remodeling mechanism and cellular players causing persistent airflow limitation in chronic obstructive pulmonary disease (COPD) remain largely elusive. We have recently demonstrated that circulating fibrocytes, a rare population of fibroblast-like cells produced by the bone marrow stroma, are increased in COPD patients during an exacerbation. It remains, however, unclear, whether fibrocytes are present in bronchial tissue of COPD patients. Objective: We aimed to quantify fibrocytes density in bronchial specimens from both control subjects and COPD patients, and to define associations with clinical, functional and computed tomography relevant parameters. Methods: 17 COPD patients and 25 control subjects with normal lung function testing and no chronic symptoms, all of them requiring thoracic surgery, were recruited. LFT and CT-scan were performed before surgery. Using co-immunostaining and image analysis, we identify CD45+ FSP1+ cells as tissue fibrocytes and quantify their density in distal and proximal bronchial specimens from the whole series. Results: Here, we demonstrate that fibrocytes are increased in both distal and proximal tissue specimens of COPD patients, compared to those of controls. The density of fibrocytes is negatively correlated with lung function parameters, such as FEV1 and FEV1/FVC, and positively with bronchial wall thickness assessed by CT scan. High density of distal bronchial fibrocytes predicts presence of COPD with a sensitivity of 83% and a specificity of 70%. Conclusions: Our results thus suggest that recruitment of fibrocytes in the bronchi may participate to lung function decline during COPD progression.