Tumour necrosis factor-alpha induction by endotoxin-containing coal mine dusts in cultures of human macrophages and its effects on pneumocyte type II cells.
Recent results indicate that tumour necrosis factor alpha (TNFalpha) may have an important role in the pathogenesis of silicosis. Supernatants of macrophages exposed to quartz and coal mine dust were tested for the presence of TNFalpha. Monocytes were isolated from peripheral blood and cultured for 10-14 days. After in vitro maturation of monocytes to cells with characteristics of macrophages, they were incubated with quartz dust DQ12 and various coal mine dusts from the Ruhr Valley for 24 hr. TNFalpha bioactivity in the supernatants of dust-treated macrophages was measured in a cytotoxicity bioassay with L929-mouse fibroblasts. Endotoxin, the lipopolysaccharide-containing cell wall component of Gram-negative bacteria, is the most important stimulator of TNFalpha induction in human macrophages. Suspensions of coal mine dusts from the Ruhr Valley and quartz dust DQ12 were therefore analysed for the presence of endotoxin by the very sensitive Limulus amoebocytes lysate test. Only a few suspensions of coal mine dusts from the Ruhr Valley contained endotoxin. Only endotoxin-containing dusts stimulated macrophages to produce TNFalpha. Incubating human pneumocytes type II (line A-549) with TNFalpha as the pure substance led to a transformation of these epithelial cells into spindle-shaped cells. This morphological transformation was accompanied by marked inhibition of pneumocyte type II proliferation.
Griwatz
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Medical Institute of Environmental Hygiene at the Heinrich-Heine University of Düsseldorf, Aufm Hennekamp 50, 40225 Düsseldorf, Germany.
Seemayer
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