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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a membrane...
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Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
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The c3-activator system: an alternate pathway of complement activation.

O Götze1, H J Müller-Eberhard

  • 1Department of Experimental Pathology, Scripps Clinic and Research Foundation, La Jolla, California 92037.

The Journal of Experimental Medicine
|October 30, 2009
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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.

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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.