1070 Contribution of bone marrow-derived fibrocytes to silicosis

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Abstract

Introduction

Exposure to free silica induces silicosis and its mechanism is less clear. Myofibroblast is regarded as a primary effector cell which is highly synthetic for collagen and lead to extensive fibrosis in lung. However, its origin is still controversial. Fibrocyte is one source of myofibroblast and proved to play a pivotal role in lung fibrogenesis, but whether fibrocyte participates in the process of silicosis is rarely reported. Therefore, the present study was designed to investigate the contribution of fibrocytes in silicosis.

Method

The rat model of silicosis was established by single intratracheal instillation of SiO2 solution (100 mg/0.5 ml/rat). HE and Masson staining were used to evaluate the histopathology and collagen deposition. Flow cytometry and immunofluorescence were performed to detect number of fibrocytes and contribution to myofibroblasts.

Results

During experimental silicosis (from week 1, 2, 3, 6, 9, 12), the number of fibrocyte is markedly increased in peripheral blood and lung tissue by using flow cytometry.Further study found that CD45+ collagen I+ fibrocyte is existed in lung tissue by using double-colour immunofluorescence analysis. Meanwhile, fibrocyte and lung type II epithelial cells contribute 15%˜35% and 9%˜21% of myofibroblasts, respectively. The trend analysis of different sources of myofibroblast during silicosis indicates that fibrocyte and lung type II epithelial cell derived myofibroblast play an important role at the early stage of silicosis (week 1 to week 3), while resident lung fibroblast-derived myofibroblast mainly do a predominant role during fibrosis formative period (week 6 to week 12).

Discussion

Taken together, these data suggest that fibrocyte is involved in the pathogenesis of silicosis and it may be useful as an indicator for disease activeity. Different sources of myofibroblasts play roles in different phases of silicosis.

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