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Evidence that C1s participates in the alternative complement pathway
Insights
The C1s subcomponent of complement C1 activates the alternative pathway under specific conditions. This finding suggests C1s plays a role in both classical and alternative complement pathway activation.
Area of Science:
- Immunology
- Complement System Biology
Background:
- The complement system comprises classical and alternative pathways crucial for innate immunity.
- C1s is a subcomponent of the classical pathway's C1 complex.
- The precise role of C1s in the alternative pathway remains incompletely understood.
Purpose of the Study:
- To investigate the potential involvement of C1s in the alternative complement pathway.
- To determine if C1s can initiate or modulate alternative pathway activation.
Main Methods:
- Experiments utilized sera genetically deficient in C2 or C4.
- Hemolytic assays were performed to assess complement component consumption.
- Immunoassays with anti-C1s antibodies and solid immunoabsorbents were employed to block or remove C1s activity.
Main Results:
- Purified C1s induced factor B conversion and C3/C5 consumption in C2- or C4-deficient sera.
- Blocking C1s activity inhibited alternative pathway activation by zymosan and cobra venom factor.
- C1s removal from C1r-deficient serum prevented alternative pathway activation by zymosan.
Conclusions:
- C1s can participate in and activate the alternative complement pathway under certain experimental conditions.
- These findings suggest C1s may be a more general component in both classical and alternative pathway activation sequences.
Abstract:
Purified C1s, subcomponent of C1, induced electrophoretic conversion of factor B and consumption of hemolytic C3 and C5 in sera genetically deficient in C2 or C4. Blocking of the hemolytic activity of C1s in C2-deficient serum by F(ab')2 anti-C1s resulted in inhibition of the alternative pathway, as indicated by the failure of zymosan or cobra venom factor to induce comsumption of C3 and C6. Zymosan also failed to activate the alternative pathway when C1s was absorbed from C1r-deficient serum using a solid immunoabsorbent. These data, showing that C1s participates in the alternative pathway under certain experimental conditions, suggest the interesing possibility that C1s is important in the activation sequence of both the classical and the alternative pathway more generally.