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Complement activation following oxidative stress
C D Collard1, R Lekowski, J E Jordan
1Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Insights
Complement activation is key in oxidative stress inflammation. Ongoing trials with complement inhibitors may offer new treatments for human diseases, but more research is needed.
Area of Science:
- Immunology
- Cellular Biology
- Pathophysiology
Background:
- The complement system plays a crucial role in inflammatory responses triggered by oxidative stress.
- Oxidative stress is implicated in various disease states, highlighting the need to understand inflammatory mediators.
- Current understanding of complement's role in disease is incomplete, particularly concerning endothelial cell activation.
Purpose of the Study:
- To explore the mechanisms of complement activation on endothelial cells following oxidative stress.
- To identify the specific ligand for mannose-binding lectin (MBL) on endothelial cells in the context of oxidative stress.
- To evaluate the potential therapeutic benefits of inhibiting MBL compared to other complement inhibitors.
Main Methods:
- Investigating complement activation pathways in cellular and animal models of oxidative stress.
- Utilizing in vitro assays to identify MBL ligands on stressed endothelial cells.
- Comparing the efficacy of MBL inhibition with established complement inhibitors (e.g., sCR1, anti-C5 mAbs) in preclinical models.
Main Results:
- Evidence suggests complement activation is a significant factor in oxidative stress-induced inflammation.
- Clinical trials are exploring the therapeutic potential of novel complement inhibitors.
- Key questions remain regarding the precise mechanisms of complement activation and MBL function in this context.
Conclusions:
- Complement inhibition shows promise as a therapeutic strategy for diseases involving oxidative stress and inflammation.
- Further research is essential to elucidate the specific roles of MBL and other complement components in endothelial cell activation.
- Understanding these pathways will guide the development of targeted therapies for human diseases.
Abstract:
It is clear that complement plays an important role in the inflammatory process following oxidative stress in cellular and animal models. Clinical trials underway with novel complement inhibitors will establish the potential therapeutic benefit of complement inhibition in human disease. For as much as we understand about the role of complement in disease states, many questions remain. How is complement activated on endothelial cells following oxidative stress? What is the ligand for MBL on endothelial cells following oxidative stress? Will inhibition of MBL provide tissue protection to the extent observed with other complement inhibitors such as sCR1 or anti-C5 mAbs? These questions and more will undoubtedly be answered in the next millennium.