Extracellular Histones Promote Pulmonary Fibrosis in Patients with Coal Workers’ Pneumoconiosis

Objective: This investigation assessed the profibrotic role that extracellular histones play in the pathogenesis of coal workers' pneumoconiosis (CWP). Methods: The correlation of extracellular histones with small opacity profusion (SOP) and transforming growth factor-beta (TGF-beta) was analyzed. The stimulating effect of extracellular histones on pulmonary fibroblast was assessed in vitro. Results: The levels of extracellular histones in plasma were positively correlated with SOP and TGF-beta in the coal miners investigated. Plasma collected from patients with CWP caused apparent lung fibroblast proliferation, while anti-H4 antibody antagonized the stimulating effect of the patient plasma by blocking histone H4. In vitro experiments showed that extracellular histones directly stimulated fibroblast proliferation. Conclusion: Consistent with our hypothesis, the concentrations of extracellular histones were indices of the severity of pulmonary fibrosis in simple CWP, and extracellular histones-targeted intervention could inhibit the proliferation of lung fibroblast.