Related Experiment Videos
Endothelin-1 secretion by alveolar macrophages in systemic sclerosis
C Odoux1, B Crestani, G Lebrun
1Institut National de la Santé et de la Recherche Médicale INSERM U408, Faculté Xavier Bichat, France.
Abstract:
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.
Insights
Alveolar macrophages from systemic sclerosis patients produce more endothelin-1 (ET-1) when stimulated. This suggests activated macrophages may contribute to lung disease in systemic sclerosis (SSc).
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Systemic sclerosis (SSc) is a fibrotic disease potentially involving activated monocytes and macrophages.
- Endothelin-1 (ET-1), a mitogen, is implicated in SSc pathogenesis.
- Alveolar macrophages (AM) and blood monocytes are key immune cells in lung inflammation.
Purpose of the Study:
- To investigate whether AM and blood monocytes from SSc patients produce more ET-1 than those from healthy individuals.
- To compare ET-1 and big ET-1 levels in plasma, bronchoalveolar lavage (BAL) fluid, and cell supernatants.
- To determine if SSc-derived immune cells exhibit altered ET-1 production in response to stimulation.
Main Methods:
- Collected plasma, BAL fluid, and isolated AM and monocytes from 13 SSc patients and 10 controls.
- Measured ET-1 and big ET-1 concentrations in biological fluids and cell culture supernatants.
- Stimulated cells with lipopolysaccharide (LPS) to assess inflammatory response and ET-1 secretion.
Main Results:
- Plasma and BAL fluid ET-1/big ET-1 levels were similar between SSc patients and controls.
- Unstimulated AM from SSc patients showed similar ET-1/big ET-1 levels compared to controls.
- LPS-stimulated AM from SSc patients produced significantly higher amounts of ET-1 and big ET-1 than controls.
- Monocyte ET-1/big ET-1 production (stimulated or unstimulated) did not differ between groups.
Conclusions:
- Alveolar macrophages from SSc patients display enhanced ET-1 and big ET-1 production upon LPS stimulation in vitro.
- This hyperresponsiveness suggests AM may play a role in the in vivo overproduction of profibrotic ET-1 in SSc lung disease.
- Blood monocytes from SSc patients did not show altered ET-1 production, indicating a cell-specific response.