Biological and Biochemical Characterisation of a “Proliferation Factor” from Quartz Dust-treated Human Macrophages

Abstract

Silicosis is a chronic fibrotic lung disease caused by inhalation of quartz-containing dusts in coal mine workers, quarriers and stone masons. The disease is characterised by an increase in collagen content of the lungs, leading to destruction of lung parenchyma and to impairment of lung function. Alveolar macrophages are the primary target for the noxious effect of quartz and coal mine dust. In the alveoli dust particles are phagocytised by alveolar macrophages and removed from the lung via the mucociliary transportation mechanism. In the case of overload, dust-laden macrophages migrate into the regional lymph node and the interstitium of the lung. Macrophages produce more than 100 biofactors or mediators that are involved in various processes of inflammation and immunological defence mechanisms (Nathan et al, 1980; Nathan, 1987). Various authors have reported that human monocytes and macrophages exposed to diverse soluble and particulate agents in vitro, release cytokines which stimulate human fibroblasts to cell multiplication (Austgulen et al, 1987; Bitterman et al., 1982; Glenn and Ross, 1981; Leslie et al., 1984; Schmidt et al, 1984; Seemayer et al, 1987, 1988). In this paper we present data on the biological and biochemical characterisation of a proliferation factor which is produced by human monocyte-derived macrophages in culture following incubation with quartz dust DQ12. The proliferation factor (PF) stimulates under serum-free conditions cell replication of quiescent human lung and dermal fibroblasts and of human pneumocyte type II (line A-549) as well as collagen synthesis of human and dermal fibroblasts.