MCP-1 SECRETION IN LUNG FROM NONSMOKING PATIENTS WITH COAL-WORKERS PNEUMOCONIOSIS

Exposure to coal dust leads to the development of coal worker's pneumo coniosis (CWP), a disease associated with an accumulation of macrophag es in the lower respiratory tract. Mechanisms controlling monocyte rec ruitment are still poorly understood. Since monocyte chemoattractant p rotein-1 (MCP-1) is recognized as a potent chemotactic factor for bloo d monocytes, we analysed the presence of MCP-1 in the pulmonary compar tment of patients with CWP. Bronchoalveolar lavage fluid (BALF) from 1 6 nonsmoking control subjects and 27 nonsmoking CWP patients (16 with simple pneumoconiosis (SP) and 11 with progressive massive fibrosis (P MF)) was analysed Alveolar macrophages (AMs) were purified by adherenc e and BALF was concentrated tenfold by lyophilization. MCP-1 was measu red 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 p atients with CWP and two control subjects. MCP-1 levels were significa ntly higher in concentrated BALF from patients with SP or PMF (median 370 and 555 pg . mL(-1), respectively) than in those from control subj ects (median 11 pg . mL(-1)) (p<0.001). Released MCP-1 in AM supernata nts was enhanced in patients with CWP (median 83 pg . mL(-1)) but comp ared to controls (median 41 pg . mL(-1)) this level did not reach sign ificance. Although significantly increased, AM counts in BALF from pat ients with CWP did not correlate with MCP-1 levels. MCP-1 levels in BA LF correlated with MCP-1 levels in AM supernatants (p=0.47; p<0.02). I n control lung specimens, MCP-1 was expressed by a few AMs, type II pn eumocytes and perivascular smooth muscle cells. CWP sections were char acterized by an increased number of AMs and mainly by the presence of fibroblasts (in the myogenic area of fibrotic lesions) and hyperplasti c type II pneumocytes, which were strongly immunostained for MCP-1. Ou r data demonstrate that: 1) patients with coal worker's pneumoconiosis have a marked pulmonary overproduction of monocyte chemoattractant pr otein-1; and 2) in addition to alveolar macrophages, fibroblasts (prob ably myofibroblasts) and hyperplastic type II pneumocytes may also be responsible for this increased level of monocyte chemoattractant prote in-1 in coal worker's pneumoconiosis.