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Complement activation by phospholipids: the interplay of factor H and C1q
- Source :
- Protein & Cell. 1:1033-1049
- Publication Year :
- 2010
- Publisher :
- Oxford University Press (OUP), 2010.
-
Abstract
- Complement proteins in blood recognize charged particles. The anionic phospholipid (aPL) cardiolipin binds both complement proteins C1q and factor H. C1q is an activator of the complement classical pathway, while factor H is an inhibitor of the alternative pathway. To examine opposing effects of C1q and factor H on complement activation by aPL, we surveyed C1q and factor H binding, and complement activation by aPL, either coated on microtitre plates or in liposomes. Both C1q and factor H bound to all aPL tested, and competed directly with each other for binding. All the aPL activated the complement classical pathway, but negligibly the alternative pathway, consistent with accepted roles of C1q and factor H. However, in this system, factor H, by competing directly with C1q for binding to aPL, acts as a direct regulator of the complement classical pathway. This regulatory mechanism is distinct from its action on the alternative pathway. Regulation of classical pathway activation by factor H was confirmed by measuring C4 activation by aPL in human sera in which the C1q:factor H molar ratio was adjusted over a wide range. Thus factor H, which is regarded as a down-regulator only of the alternative pathway, has a distinct role in downregulating activation of the classical complement pathway by aPL. A factor H homologue, β2-glycoprotein-1, also strongly inhibits C1q binding to cardiolipin. Recombinant globular domains of C1q A, B and C chains bound aPL similarly to native C1q, confirming that C1q binds aPL via its globular heads.
- Subjects :
- chemical and pharmacologic phenomena
Biochemistry
Complement factor B
Mice
Classical complement pathway
fluids and secretions
immune system diseases
Drug Discovery
Animals
Humans
skin and connective tissue diseases
Complement Activation
neoplasms
Phospholipids
biology
Complement component 2
Complement C1q
Cell Biology
Complement system
Complement Factor H
Immunoglobulin G
Lectin pathway
Factor H
Alternative complement pathway
biology.protein
Protein Binding
Research Article
Biotechnology
Complement control protein
Subjects
Details
- ISSN :
- 16748018 and 1674800X
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Protein & Cell
- Accession number :
- edsair.doi.dedup.....648ce4f4d92fa556d335986ed497f507