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Critical Role of the C-Terminal Domains of Factor H in Regulating Complement Activation at Cell Surfaces
- Source :
- The Journal of Immunology. 177:6308-6316
- Publication Year :
- 2006
- Publisher :
- The American Association of Immunologists, 2006.
-
Abstract
- The plasma protein factor H primarily controls the activation of the alternative pathway of complement. The C-terminal of factor H is known to be involved in protection of host cells from complement attack. In the present study, we show that domains 19–20 alone are capable of discriminating between host-like and complement-activating cells. Furthermore, although factor H possesses three binding sites for C3b, binding to cell-bound C3b can be almost completely inhibited by the single site located in domains 19–20. All of the regulatory activities of factor H are expressed by the N-terminal four domains, but these activities toward cell-bound C3b are inhibited by isolated recombinant domains 19–20 (rH 19–20). Direct competition with the N-terminal site is unlikely to explain this because regulation of fluid phase C3b is unaffected by domains 19–20. Finally, we show that addition of isolated rH 19–20 to normal human serum leads to aggressive complement-mediated lysis of normally nonactivating sheep erythrocytes and moderate lysis of human erythrocytes, which possess membrane-bound regulators of complement. Taken together, the results highlight the importance of the cell surface protective functions exhibited by factor H compared with other complement regulatory proteins. The results may also explain why atypical hemolytic uremic syndrome patients with mutations affecting domains 19–20 can maintain complement homeostasis in plasma while their complement system attacks erythrocytes, platelets, endothelial cells, and kidney tissue.
- Subjects :
- Binding Sites
Erythrocytes
Complement component 2
Erythrocyte Membrane
Immunology
Complement factor I
Biology
Binding, Competitive
Hemolysis
Recombinant Proteins
Protein Structure, Tertiary
Cell biology
Complement system
Complement Factor H
Factor H
Complement C3b
biology.protein
Alternative complement pathway
Animals
Humans
Immunology and Allergy
Anaphylatoxin
Complement Activation
Decay-accelerating factor
Complement control protein
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 177
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....2dbf7c1bac965be188aafd6f456f92e7