Detection of Alveolar Fibrocytes in Idiopathic Pulmonary Fibrosis and Systemic Sclerosis

Raphael Borie,Joelle Marchal-Somme,Bruno Crestani,Kiet Tiev,Sophie Phin,Paul Soler,Marie-Pierre Debray,Aurélie Fabre,Christophe Quesnel,Monique Dehoux,Marcel Bonay

doi:10.1371/journal.pone.0053736

Abstract

BackgroundFibrocytes are circulating precursors for fibroblasts. Blood fibrocytes are increased in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to determine whether alveolar fibrocytes are detected in broncho-alveolar lavage (BAL), to identify their prognostic value, and their potential association with culture of fibroblasts from BAL.MethodsWe quantified fibrocytes in BAL from 26 patients with IPF, 9 patients with Systemic Sclerosis(SSc)-interstitial lung disease (ILD), and 11 controls. BAL cells were cultured to isolate alveolar fibroblasts.ResultsFibrocytes were detected in BAL in 14/26 IPF (54%) and 5/9 SSc patients (55%), and never in controls. Fibrocytes were in median 2.5% [0.4–19.7] and 3.0% [2.7–3.7] of BAL cells in IPF and SSc-ILD patients respectively. In IPF patients, the number of alveolar fibrocytes was correlated with the number of alveolar macrophages and was associated with a less severe disease but not with a better outcome. Fibroblasts were cultured from BAL in 12/26 IPF (46%), 5/9 SSc-ILD (65%) and never in controls. The detection of BAL fibrocytes did not predict a positive culture of fibroblasts.ConclusionFibrocytes were detected in BAL fluid in about half of the patients with IPF and SSc-ILD. Their number was associated with less severe disease in IPF patients and did not associate with the capacity to grow fibroblasts from BAL fluid.

Highlights

Lung fibrosis is a common trait of different diseases with different etiologies and different pathophysiological pathways
Fibrocytes have been implicated in the pathophysiology of other fibrotic lung disorders, such as interstitial lung disease associated with systemic sclerosis (SSc-ILD), where fibrocytes have been shown to be increased in the peripheral blood and to accumulate in the lung [9]
In patients with acute lung injury (ALI), we described that fibrocytes could be detected in bronchoalveolar lavage (BAL) in almost all patients and that BAL fibrocyte percentage was independently associated with increased mortality [10]

Summary

Introduction

Lung fibrosis is a common trait of different diseases with different etiologies and different pathophysiological pathways. In experimental models of acute lung injury (ALI), bonemarrow derived cells have been shown to be recruited to the lung and to contribute to normal and pathologic repair [3]. Among these cells, fibrocytes are mesenchymal progenitors derived from hematopoıetic precursors, which co-express leukocyte (CD45+). Fibrocytes are implicated in a wide variety of focal and diffuse remodeling disorders [5], in the skin, lung, liver, kidney, pancreas or in atherosclerosis [6] The fibrocytes, and their CD14 positive mononuclear precursors [6], are recruited from the blood to organs through multiple chemokine signaling pathways including the CCL2/ CCR2 and the CXCL12/CXCR4 pathways [6]. The aim of this study was to determine whether alveolar fibrocytes are detected in bronchoalveolar lavage (BAL), to identify their prognostic value, and their potential association with culture of fibroblasts from BAL

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