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 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.
Odoux
C
C
Institut National de la Santé et de la Recherche Médicale INSERM U408, Faculté Xavier Bichat, France.
Crestani
B
B
Lebrun
G
G
Rolland
C
C
Aubin
P
P
Seta
N
N
Kahn
M F
MF
Fiet
J
J
Aubier
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D017563:Lung Diseases, Interstitial / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011446:Prospective Studies; D011498:Protein Precursors / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000503:physiopathology*
D019332:Endothelin-1; D016232:Endothelins; D008070:Lipopolysaccharides; D011498:Protein Precursors