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Quantification of non-activated (native) complement component C9 synthesized by alveolar macrophages from patients
H B Pettersen1, E Johnson, P Garred
1Department of Internal Medicine, University of Trondheim, Norway.
Insights
Alveolar macrophages (AM) from sarcoidosis patients produce more complement C9 than those from healthy individuals. This suggests a potential role for C9 in sarcoidosis pathogenesis.
Area of Science:
- Immunology
- Pulmonology
- Complement System Biology
Background:
- Sarcoidosis pathogenesis may involve increased complement production by alveolar macrophages (AM).
- The complement system, particularly C9, plays a role in inflammatory processes.
Purpose of the Study:
- To investigate whether AM from sarcoidosis patients produce quantitatively more C9 in vitro compared to AM from healthy controls.
- To explore the potential involvement of C9 in the pathogenesis of sarcoidosis.
Main Methods:
- Alveolar macrophages (AM) were isolated from 16 sarcoidosis patients and 7 healthy controls.
- Cells were cultured under serum-free conditions for up to 72 hours.
- C9 production was quantified using an enzyme immunoassay with a monoclonal antibody (M1) specific for non-activated C9.
Main Results:
- Quantitative C9 production was detected in the medium of 10 out of 16 sarcoidosis patients.
- No detectable levels of C9 were found in the seven healthy controls.
- Activated C9 was present in all patients and most controls, indicating complement system activation.
Conclusions:
- Sarcoidosis AM demonstrate greater C9 production in vitro compared to AM from healthy individuals.
- Increased C9 production by AM may contribute to the pathogenesis of sarcoidosis.
- Further research is warranted to elucidate the specific role of C9 in sarcoidosis.
Abstract:
Alveolar macrophages (AM) from sarcoidosis patients synthesize the functional alternative and terminal pathways of complement, and increased complement production may be one of multiple factors in the pathogenesis of sarcoidosis. We thus examined whether AM from sarcoidosis patients produced quantitatively more C9 in vitro than AM from healthy controls. AM from 16 patients with active sarcoidosis and seven healthy controls were cultured under serum-free conditions for 6, 12, 24, 48, or 72 h. A quantitative production of C9 was found in the harvested medium in 10 of 16 sarcoidosis patients. There were no detectable levels of C9 in the seven controls. Activated C9 was found in all patients and in the majority of the controls. C9 was quantified by an enzyme immunoassay based on a monoclonal antibody (M1) to non-activated C9. Our results indicate greater production of C9 by sarcoidosis AM than by their healthy counterparts.