ENDOTHELIN-1 SECRETION BY ALVEOLAR MACROPHAGES IN SYSTEMIC-SCLEROSIS

Endothelin-1 (ET-1), a potent fibroblast/smooth muscle cells mitogen, has been implicated in the pathogenesis of systemic sclerosis lung dis ease (SSc). Since monocytes and macrophages are thought to be activate d in SSc, we hypothesized that alveolar macrophages (AM) and their pre cursors blood monocytes from patients with SSc produced more ET-1 than cells from healthy subjects. ET-1 and big ET-l concentrations were me asured in plasma, in bronchoalveolar lavage (BAL) fluids and in cell c ulture supernatants from monocytes and alveolar macrophages derived fr om 13 patients with definite SSc with lung involvement and from 10 con trol subjects. Plasma and BAL fluid ET-1 and big ET-1 levels were simi lar in both controls and patients with SSc. ET-1 and big ET-1 concentr ations in unstimulated alveolar macrophage supernatants were similar i n both groups. In contrast, LPS-stimulated alveolar macrophages from p atients with SSc secreted higher amounts of ET-1 and big ET-1 than con trol subjects. ET-1 and big ET-1 concentrations in monocyte supernatan ts (either LPS-stimulated or not) were not different in patients and c ontrols. These results show that AM from patients with SSc are hyperre sponsive to LPS in vitro in terms of ET-1 and big ET-1 production and suggest that AM could participate in vivo in the overproduction of thi s potentially profibrotic mediator in patients with SSc.