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06:29
Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
The c3-activator system: an alternate pathway of complement activation.
1Department of Experimental Pathology, Scripps Clinic and Research Foundation, La Jolla, California 92037.
The Journal of Experimental Medicine
|October 30, 2009
Summary
A novel complement activation pathway involves C3PA, a protein that acts as a precursor to the C4,2 analogue. This pathway, activated by various substances, cleaves C3, impacting immune responses like bacterial killing and hemolysis.
Area of Science:
- Immunology
- Biochemistry
Background:
- Evidence suggests a second complement activation mechanism analogous to C1, C2, and C4.
- C3PA (complement C3 proactivator) is identified as a precursor to the C4,2 analogue.
Purpose of the Study:
- To elucidate the role of C3PA in a newly identified complement activation pathway.
- To characterize the activation products and functions of C3PA.
Main Methods:
- Serum treatment with polysaccharides and immunoglobulin aggregates.
- Analysis of protein fragments using electrophoresis and molecular weight determination.
- Assays for C3 cleavage and assessment of bactericidal and hemolytic activity.
Main Results:
- C3PA (80,000 MW) is cleaved by C3PA convertase into a 60,000 MW C3 activator and a 20,000 MW peptide.
- Activation is triggered by polysaccharides (endotoxins, yeast, inulin, agar) and immunoglobulin aggregates (IgA, IgG).
- Serum depleted of C3PA showed reduced E. coli bactericidal and increased hemolytic activity.
Conclusions:
- C3PA is a key component of an alternative complement activation pathway.
- The C3-activator system plays a significant role in immune responses, influencing both bacterial killing and hemolysis.
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