Objective: To explore the role of extracellular
histones in the pathogenesis of
coal worker's pneumoconiosis (CWP) , the relationship of extracellular
histones in plasma with
pulmonary fibrosis caused by
coal mine dust was analyzed, and the stimulating effect of extracellular
histones on fibroblast proliferation was studied. Methods: In May 2019, a total of 220
coal mine dust exposure workers (including
coal miners and CWP patients) who visited the
occupational disease outpatient department of Peking University Third Hospital from 2012 to 2015 were enrolled in the study. According to the classification of small opacity profusion (SOP) in chest radiograph for
pneumoconiosis diagnosis (category 0, 1, 2, 3) , 61
coal miners were in category 0 SOP, 65
coal miners were in category 1 SOP, 56
coal miners were in category 2 SOP and 38
coal miners were in category 3 SOP. The plasma levels of extracellular
histone H4 and
platelet-derived growth factor (PDGF) were measured by
enzyme-linked
immunosorbent assay (ELISA) kit. The stimulating effects of CWP patients' plasma and calf thymus
histones (CTHs) on fibroblast and the antagonizing effect of anti-H4 antibody were investigated by fibroblast proliferation experiment in vitro. Results: Among the study subjects, there were 195 males (88.6%, 195/220) and 25 females (11.4%, 25/220) , age (55.1±7.2) years,
coal mine dust exposure time (16.3±4.4) years. The plasma concentrations of
histone H4 in the
coal miners with category 0, 1, 2 and 3 SOP were (3.92±1.75) 、(9.84±4.17) 、(14.35±5.52) and (17.83±7.69) μg/ml, respectively. There were significant differences among the four groups (P<0.01) . The plasma level of
histone H4 was positively correlated with the plasma level of PDGF in the
coal miners (r=0.769, P<0.01) . Compared with healthy control plasma group, the cell proliferation percentages of patients' plasma group (272%±87%) and CTH group (283%±84%) were significantly increased (P<0.05) . Compared with patients' plasma group, the cell proliferation percentage of patients' plasma+anti-H4 antibody group (185%±66%) was significantly decreased (P<0.05) . Compared with CTH group, the cell proliferation percentage of CTH+anti-H4 antibody group (167%±59%) was significantly decreased (P<0.05) . Conclusion: Extracellular
histones in plasma are associated with
pulmonary fibrosis in patients with CWP. Studies in vitro have shown that extracellular
histones can promote proliferation of pulmonary fibroblasts. It is suggested that extracellular
histones can be important
biomarkers for
pulmonary fibrosis caused by
coal mine dust.