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Endogenous association of decay-accelerating factor (DAF) with C4b and C3b on cell membranes
Insights
Decay-accelerating factor (DAF) binds to complement fragments C4b and C3b on cell surfaces. This interaction prevents the formation of C3 convertases, regulating the complement system.
Area of Science:
- Immunology
- Complement System Biology
Background:
- Decay-accelerating factor (DAF) is a membrane glycoprotein that regulates the complement system.
- DAF inhibits the formation of C3 convertases in both the classic and alternative complement pathways.
Purpose of the Study:
- To identify the ligand for DAF on cells undergoing complement attack.
- To elucidate the mechanism by which DAF regulates complement activation.
Main Methods:
- Utilized a homobifunctional cross-linking reagent to probe for DAF interactions.
- Analyzed the formation of complexes between DAF and complement fragments on erythrocytes.
Main Results:
- DAF forms complexes with C4b and C3b deposited on erythrocytes.
- DAF does not form complexes with the degradation products C4d or C3dg.
- DAF's action is reversible and does not alter the structure of C4b or C3b.
Conclusions:
- DAF functions by competitively inhibiting the binding of C2 or factor B.
- This inhibition prevents the assembly of C3 convertases, thereby regulating complement activation.
Abstract:
Decay-accelerating factor (DAF) is a membrane glycoprotein found on various cells that are in contact with complement. It inhibits the formation of the C3 convertases of the complement system, both the classic (C4b2a) and alternative (C3bBb) pathways. In this investigation, we used a homobifunctional cross-linking reagent to search for a DAF ligand on the surface of cells subjected to complement attack. We found that DAF forms complexes with C4b and C3b deposited on the same erythrocytes, but not with the physiologic degradation products of these complement fragments, that is, C4d or C3dg. Taken together with prior observations that DAF action is reversible, and DAF does not affect the structure of C4b or C3b, these findings suggest that DAF functions by competitively inhibiting the uptake of C2 or factor B, and preventing the assembly of the C3 convertases.