Mechanisms of fibrosis in coal workers' pneumoconiosis. Increased production of platelet-derived growth factor, insulin-like growth factor type I, and transforming growth factor beta and relationship to disease severity.
To identify the clinical relevance of cytokines involved in the development of lung fibrosis observed in patients with coal workers' pneumoconiosis (CWP), we investigated the BAL fluid contents and AM secretions of three mediators that modulate fibroblast growth: platelet-derived growth factor (PDGF), Type I insulin-like growth factor (IGF-I), and transforming growth factor Type beta (TGF-beta). Our study population consisted of 25 patients with CWP (16 simple pneumoconiosis, SP, 9 progressive massive fibrosis, PMF, 9 control subjects, and 6 patients with idiopathic pulmonary fibrosis (IPF). The fibrotic potency of AM supernatants was also tested for their ability to promote the growth of a human lung fibroblast cell line appreciated by [3H]-thymidine incorporation. PDGF and IGF-I concentrations were increased in BAL fluids of patients with PMF compared with SP and control subjects, whereas TGF-beta concentration was significantly higher in BAL fluid of patients with SP compared with PMF and control subjects. PDGF, IGF-I, and TGF-beta concentrations in AM supernatants followed the same profile observed in BAL fluids, suggesting that AM is one of the main cell sources of PDGF, IGF-I, and TGF-beta in the lung of pneumoconiotic patients. After treatment by acidification, which activated the latent form of TGF-beta, AM from patients with SP induced an inhibition of [3H]-thymidine incorporation and fibroblast growth was restored after neutralization of TGF-beta by specific antibodies. In contrast, AM supernatants from patients with PMF and IPF promoted the proliferation of fibroblasts and treatment by acidification did not modify this effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Vanhee
D
D
Laboratoire de Pathologie Immunoallergique Respiratoire et Cellules Inflammatoires, INSERM Unité 416, Institut Pasteur, Lille, France.
Gosset
P
P
Wallaert
B
B
Voisin
C
C
Tonnel
A B
AB
D000368:Aged; D000704:Analysis of Variance; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D003032:Coal Mining / Q000706:statistics & numerical data; D004391:Dust / Q000009:adverse effects; D005602:France / Q000453:epidemiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D008903:Minerals / Q000009:adverse effects; D010982:Platelet-Derived Growth Factor / Q000032:analysis* / Q000378:metabolism; D011009:Pneumoconiosis / Q000150:complications* / Q000453:epidemiology / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000378:metabolism
D004391:Dust; D008903:Minerals; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I