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Exposure to coal dust leads to the development of coal worker's pneumoconiosis (CWP), a disease associated with an accumulation of macrophages in the lower respiratory tract. Mechanisms controlling monocyte recruitment are still poorly understood. Since monocyte chemoattractant protein-1 (MCP-1) is recognized as a potent chemotactic factor for blood monocytes, we analysed the presence of MCP-1 in the pulmonary compartment of patients with CWP. Bronchoalveolar lavage fluid (BALF) from 16 nonsmoking control subjects and 27 nonsmoking CWP patients (16 with simple pneumoconiosis (SP) and 11 with progressive massive fibrosis (PMF)) was analysed. Alveolar macrophages (AMs) were purified by adherence and BALF was concentrated tenfold by lyophilization. MCP-1 was measured in BALF and in 3 h AM supernatants using a sandwich enzyme-linked immunosorbent assay (ELISA). The localization of MCP-1 in lung tissue was determined by immunohistochemistry on tissue sections from three patients with CWP and two control subjects. MCP-1 levels were significantly higher in concentrated BALF from patients with SP or PMF (median 370 and 555 pg x mL-1, respectively) than in those from control subjects (median 11 pg x mL-1) (p<0.001). Released MCP-1 in AM supernatants was enhanced in patients with CWP (median 83 pg x mL-1) but compared to controls (median 41 pg x mL-1) this level did not reach significance. Although significantly increased, AM counts in BALF from patients with CWP did not correlate with MCP-1 levels. MCP-1 levels in BALF correlated with MCP-1 levels in AM supernatants (p=0.47; p<0.02). In control lung specimens, MCP-1 was expressed by a few AMs, type II pneumocytes and perivascular smooth muscle cells. CWP sections were characterized by an increased number of AMs and mainly by the presence of fibroblasts (in the myogenic area of fibrotic lesions) and hyperplastic type II pneumocytes, which were strongly immunostained for MCP-1. Our data demonstrate that: 1) patients with coal worker's pneumoconiosis have a marked pulmonary overproduction of monocyte chemoattractant protein-1; and 2) in addition to alveolar macrophages, fibroblasts (probably myofibroblasts) and hyperplastic type II pneumocytes may also be responsible for this increased level of monocyte chemoattractant protein-1 in coal worker's pneumoconiosis.

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)