Am. J. Respir. Crit. Care Med.,
Volume 156, Number 5, November 1997, 1429-1435
Endothelin-1 Secretion by Alveolar Macrophages
in Systemic Sclerosis
CHRISTINE
ODOUX,
BRUNO
CRESTANI,
GAËLLE
LEBRUN,
CORINNE
ROLLAND,
PHILIPPE
AUBIN,
NATHALIE
SETA,
MARCEL-FRANCIS
KAHN,
JEAN
FIET,
and
MICHEL
AUBIER
Institut National de la Santé et de la Recherche Médicale INSERM U408, Faculté Xavier Bichat; Laboratoire de Biologie Hormonale,
Hôpital Saint Louis; Service de Biochimie A, Service de Rhumatologie, Hôpital Bichat; Assistance publique, Hôpitaux de Paris, France
Endothelin-1 (ET-1), a potent fibroblast/smooth muscle cells mitogen, has been implicated in the
pathogenesis of systemic sclerosis lung disease (SSc). Since monocytes and macrophages are thought
to be activated in SSc, we hypothesized that alveolar macrophages (AM) and their precursors blood
monocytes from patients with SSc produced more ET-1 than cells from healthy subjects. ET-1 and big
ET-1 concentrations were measured in plasma, in bronchoalveolar lavage (BAL) fluids and in cell culture supernatants from monocytes and alveolar macrophages derived from 13 patients with definite SSc with lung involvement and from 10 control subjects. Plasma and BAL fluid ET-1 and big ET-1 levels were similar in both controls and patients with SSc. ET-1 and big ET-1 concentrations in unstimulated alveolar macrophage supernatants were similar in both groups. In contrast, LPS-stimulated alveolar macrophages from patients with SSc secreted higher amounts of ET-1 and big ET-1 than
control subjects. ET-1 and big ET-1 concentrations in monocyte supernatants (either LPS-stimulated
or not) were not different in patients and controls. These results show that AM from patients with
SSc are hyperresponsive 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 this potentially profibrotic mediator in patients with
SSc.
