Abstract

BackgroundMyofibroblasts, proposed as being derived from circulating fibrocytes, are considered to be important cells in thickening of the basement membrane in patients with asthma. We have studied the correlation of tissue fibrocyte levels to basement membrane thickness and the presence of fibrocytes in bronchoalveolar lavage fluid (BALF) in steroid-naive patients with mild asthma and controls.MethodsPatients with mild asthma (n = 9) were recruited and divided into two categories based on whether or not fibroblast-like cells could be established from BALF. Non-asthmatic healthy subjects (n = 5) were used as controls. Colocalization of the fibrocyte markers CD34, CD45RO, procollagen I, and α-smooth muscle actin (α-SMA) were identified in bronchial biopsies from patients and controls by confocal microscopy. Kruskall-Wallis method was used to calculate statistical significance and Spearman coefficient of rank correlation was used to assess the degree of association.ResultsIn patients with BALF fibroblasts, a 14-fold increase of tissue cells expressing CD34/CD45RO/α-SMA and a 16-fold increase of tissue cells expressing CD34/procollagen I was observed when compared to controls (p < 0.05). In contrast, patients without BALF fibroblasts displayed a 2-fold increase when compared to controls (p < 0.05). Fibrocytes were localized close to the basement membrane which was significantly thicker in patients with BALF fibroblasts when compared to the other two groups of subjects. Furthermore, basement membrane thickness could be correlated to the number of fibrocytes in tissue (r = 0.711). Fibroblasts-like cells were cultured from BALF where 17.6% of these cells expressed CD34, CD45RO and α-SMA.ConclusionThese findings indicate a correlation between recruited fibrocytes in tissue and thickness of basement membrane. Fibroblast progenitor cells may therefore be important in airway remodeling in steroid-naive patients with mild asthma.

Highlights

  • Myofibroblasts, proposed as being derived from circulating fibrocytes, are considered to be important cells in thickening of the basement membrane in patients with asthma

  • These findings suggest that fibrocytes are important key cells in airway remodeling in patients with allergen-induced asthma and in vivo models, fibrocytes have not been studied in steroid-naive patients with mild asthma

  • We have previously shown that activated fibroblasts-like cells may be cultured from bronchoalveolar lavage fluid (BALF) from a sub-group of patients with mild asthma accompanied by elevated levels of eosinophils [16]

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Summary

Introduction

Myofibroblasts, proposed as being derived from circulating fibrocytes, are considered to be important cells in thickening of the basement membrane in patients with asthma. Considering the importance of fibroblasts in airway remodeling it is important to establish the possible origins of these cells which today are unclear It has been postulated in several in vivo models and in patients with allergen-induced asthma that lung tissue repair and regeneration after injury involve the selective recruitment of circulating fibroblast progenitor cells, termed fibrocytes [7,8,9]. TGF-β1 is an important inducer of fibrosis and may in addition stimulate fibroblasts in tissue and induce the differentiation of fibrocytes into myofibroblast-like cells with elevated production of extracellular matrix components [14,15] These findings suggest that fibrocytes are important key cells in airway remodeling in patients with allergen-induced asthma and in vivo models, fibrocytes have not been studied in steroid-naive patients with mild asthma

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