title: Human factor H and C4b-binding protein serve as factor I-cofactors both encompassing inactivation of C3b and C4b.
abstract: Human factor H in the complement (C) system has been characterized as a decay-accelerator for the alternative C pathway C3 convertase and a cofactor for factor I-mediated inactivation of C3b. The current concept is that it does not serve as a C4b-inactivating cofactor. In the present study, we demonstrated that in fluid-phase, factor H and Factor I can cleave methylamine-treated C4(C4ma), a C4b analogue, to C4d, regardless of its isotype. The buffer pH and ionic strength were critical factors for the C4ma cleavage, which proceeded at around pH 6.0 and low conductivity around 3.0 mS. Similar results were obtained with fluid-phase C4b. Cell-bound C4b, however, did not undergo factor I-mediated inactivation by factor H. Hence, all of the human cofactors reported to date can mediate factor I-mediated cleavage of both C3b and C4b at least in the fluid-phase.
authors.affiliation: Department of Immunology, Center for Adult Diseases Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Seya
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Masaki
authors.forename: C
authors.initials: C
authors.lastname: Ichihara-Itoh
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Nagasawa
mesh_terms: D002352:Carrier Proteins / Q000276:immunology*; D003180:Complement C3b Inactivator Proteins / Q000276:immunology*; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017242:Complement Factor H / Q000276:immunology*; D017244:Complement Factor I / Q000276:immunology*; D003169:Complement Inactivator Proteins / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: C493495:CFH protein, human; D002352:Carrier Proteins; D003180:Complement C3b Inactivator Proteins; D003181:Complement C4; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D010446:Peptide Fragments; C033860:complement C4c; D015935:Complement C4b; C032261:complement C4d; D017242:Complement Factor H; D017244:Complement Factor I