The myofibroblast in pulmonary fibrosis displays distinct functional characteristics, depending on its source of origin

Introduction Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, with an extremely poor prognosis. The key effector cell is the myofibroblast, characterised by alpha smooth muscle actin (α-SMA) expression. Recruitment of myofibroblasts is from three potential sources: resident fibroblasts, fibrocytes and epithelial cells. However, the relative contribution of each of these sources remains unclear. Methods Primary human normal pulmonary fibroblasts, IPF fibroblasts, fibrocytes and small airway epithelial cells were transitioned to myofibroblasts using transforming growth factor-beta (TGF-β) and tumour necrosis factor alpha (TNF-α). Real time PCR, western blotting and immunofluorescence confirmed the myofibroblast transition. A soluble collagen assay (sircol®) and proliferation assay (bromodeoxyuridine/BrdU) was then performed to assess functional characteristics of the myofibroblast populations. Results In terms of soluble collagen production, myofibroblasts derived from IPF fibroblasts are most responsive to TGF-β and TNF-α (mean soluble collagen pre treatment 5.2μg/ml, post treatment 10.5μg/ml), followed in turn by fibrocytes, epithelial cells and normal fibroblasts. However, it is the myofibroblast derived from the fibrocyte that produces the highest amount of soluble collagen (17.7μg/ml). In terms of proliferation, it is the normal fibroblasts that are most proliferative, followed by epithelial cells, IPF fibroblasts and fibrocytes. Conclusion The myofibroblast in pulmonary fibrosis differs in terms of soluble collagen production and proliferation, depending on its source of origin.